Committee on Human Research Guidelines and Procedures The Johns Hopkins University School of Hygiene and Public Health Table of Contents PREFACE...................................................... 1 AUTHORITY.................................................... 2 INTRODUCTION................................................. 3 DEFINITIONS.................................................. 4 I. STATEMENT OF GENERAL POLICY OF THE SCHOOL OF HYGIENE AND PUBLIC HEALTH FOR THE PROTECTION OF HUMAN SUBJECTS ........................................................ 6 A. Ethical Principles................................. 6 B. Institutional Policy............................... 6 C. Committee Membership............................... 8 D. Committee Staff.................................... 9 E. Committee Meetings................................. 9 F. Committee Records.................................. 9 II. RESPONSIBILITY OF PRINCIPAL INVESTIGATORS AND DEPARTMENT HEADS FOR SUBMITTING A RESEARCH APPLICATION TO THE COMMITTEE ON HUMAN RESEARCH ........................................................ 10 A. Procedures for Submitting New Application.......... 10 1. CHR Application Form.......................... 11 2. Research Summary.............................. 11 3. Research Protocol or Grant Application........ 11 4. Disclosure Statement and/or Informed Consent Form.......................................... 11 5. Other Relevant Documents (as appropriate)..... 12 a. Questionnaire or Data Gathering Form..... 12 b. Research Involving Interviews in the Greater Baltimore Area........................... 12 C. Research Involving Drugs, Radiation, Pregnant Women, Fetal Tissue or Biohazardous Agents................................... 13 d. International Research Studies........... 13 e. Collaborative Institutional Studies...... 13 B. Research involving Johns Hopkins Hospital Patients. 14 C. New Applications Requiring Special CHR Action...... 14 1. Emergency Review and Approval................... 14 a. Type of Activities Which Qualify:........ 14 b. The Following Documents Should be submitted................................ 14 C. Committee Action......................... 15 2. Expedited Review................................ 15 a. Federal Regulations...................... 15 b. Policy of the Committee on Human Research 16 3. Research Exempted From Full CHR Review........ 18 a. Federal Regulations...................... 18 b. Policy of the Committee on Human Research 19 4. Research Involving Special Study Populations. 20 Minors........................................ 20 a. Federal Regulations...................... 20 b. Policy of the Committee on Human Research 20 3) Consent/Assent........................... 22 a) Children younger than 5 years....... 22 b) Children between the ages of 5 and 12 years:.............................. 22 c) Children between the ages of 12 and 16 years:.............................. 22 d) Children between the ages of 16 and 18 years:.............................. 23 e) Studies involving children of ALL ages................................ 23 (4) Wards of the State............................ 23 Prisoners.......................................... 23 a. Federal Regulations........................... 24 b. Policy of the Committee on Human Research..... 25 Pregnant Women, Fetuses, Human In Vitro Fertilization .............................................. 25 a. Federal Regulations........................... 25 b. Policy of the Committee on Human Research..... 26 Institutionalized as Mentally Disabled............. 26 a. Federal Regulations........................... 26 Students as Research Subjects...................... 26 b. Recruitment of Students as Subjects for Specific Research Projects............................. 27 Self-Experimentation............................... 27 E. General Assurance Statement of Compliance for Federal Grants and Contracts............................... 27 F. Proposed Modifications of the Original Protocol.... 28 1. Renewal Applications.......................... 28 2. New Information Concerning Effects on Human Subjects...................................... 29 3. Disposition of the Data for Inactive Studies.. 29 G. Subpoena of Research Records....................... 30 III. Procedures for Committee Review of Research Proposals Involving Human Subjects................................ 30 A. General Information................................ 30 1. Schedule of Meetings.......................... 30 2. Distribution of Materials to Members.......... 30 3. Voting by the Committee....................... 31 B. Review of New Applications......................... 32 1. Staff Responsibilities........................ 32 a. Standard Research Proposals.............. 32 b. Exempt Research.......................... 32 C. Expedited Research....................... 32 2. Standard Review Requiring Full Committee Approval...................................... 33 3. Emergency Review and Approval................. 34 4. Expedited Review.............................. 35 a. Research Which Qualifies for Expedited Action................................... 36 b. Procedures for Committee Approval........ 37 C. Full Committee Review................... 38 5. Research Exempted From Committee.............. 38 b. Policy of the Committee on Human Research................................. 39 C. Full Committee Recommendations on Research Reviewed by CHR................. 40 d. Communications from the Committee on Human Research........................... 41 e. Appeal of Committee on Human Research Decisions................................ 43 f. Continuing Review of Applications........ 43 (1) Changes After Approval.............. 43 (2) Annual Renewal...................... 43 3. Periodic Review............................... 44 IV. General Requirements for Informed Consent; Privacy and Confidentiality; Assessing Risk/Benefit ............................................................. 45 A. Informed Consent................................... 45 1. Federal Regulations........................... 45 a. General Policy........................... 45 b. Disclosure............................... 45 C. Documentation............................ 46 2. Policy of the Committee on Human Research..... 47 a. General Policy........................... 47 b. Disclosure............................... 48 C. Documentation............................ 48 (1) Substitution of Oral Consent for Written consent:.................... 48 (2) Implied Consent:.................... 49 (3) Auditor Witness-Observers of Consent Process:............................ 49 (4) Informed Consent and International Research:........................... 50 (5) Informed Consent and Minors, the Mentally Disabled and Prisoners:.... 51 3. General Guidelines for Preparing Disclosure /Informed Consent Statement for Subjects to Participate in Research Projects.............. 51 B. Privacy and Confidentiality........................ 53 1. Federal Regulations........................... 53 2. Policy of the Committee on Human Research..... 53 a. Access to Records, Data Collection Coding, Data processing, Editing, Analysis....... 54 b. Presentation and Publication of the Results of the Research.......................... 54 C. Maintenance and Retention of Information After the Proposed Research Has Been Completed................................ 54 3. Suggested Procedures for Maintaining Confidentiality............................... 55 a. One method for protecting the identity of study subjects........................... 55 b. Safeguarding Confidentiality of Records.. 55 C. In discussing confidentiality in the consent statement................................ 57 d. General Guidelines for Safeguarding Confidentiality.......................... 57 (1) Studies Involving Surveys:.......... 57 (2) Studies Involving the Use of Records: 57 C. Risk-Benefit Considerations........................ 58 1. Federal Regulations........................... 58 2. Policy of the Committee on Human Research..... 58 DECLARATION OF HELSINKI...................................... 60 PREFACE The School of Hygiene and Public Health of the Johns Hopkins University is deeply concerned with the protection of the rights, well-being, and personal privacy of individuals who participate in research and other related activities, as well as with maintaining quality in the pursuit of scientific knowledge. The faculty and student body of Ile School of Hygiene and Public Health acknowledge their responsibility for protecting the rights of research subjects and for avoiding any element of coercion or intimidation in recruiting subjects for participation in research activities. A set of procedures has been established by the School to allow faculty and students to provide appropriate assurances that any research activity involving human subjects will comply with the policies of the School, the Code of Federal Regulations, Part 46, Title 45, as amended, for the "Protection of Human subjects in Biomedical Research,"and the laws of the State of Maryland. In carrying out this responsibility, the Administration of the School of Hygiene and Public Health will make every effort to acquaint faculty, students and administrators with the policy and procedures of this institution. This Manual is designed to provide guidance to research investigators, administrators, and members of the Committee on Human Research in discharging their responsibilities. 1 Alfred Sommer, M.D. Dean AUTHORITY The Johns Hopkins School of Hygiene and Public Health require that no research project involving human subjects may be initiated until it has been reviewed by the Committee on Human Research and approved or certified to be exempt from full committee review. The Committee on Human Research (CHR) is appointed by the Dean as the committee which serves as the Institutional Review Board (IRB) for the Johns Hopkins University School of Hygiene and Public Health. The committee is comprised of qualified and professional competent individuals representing diverse disciplines and professions at the School of Hygiene and Public Health and from the community and is charged with the responsibility of review and approval of research projects conducted by Johns Hopkins University School of Hygiene faculty (full or part-time). The Committee's major function is to identify, discuss and resolve ethical issues which relate to the safeguarding of the rights and welfare of human subjects participating in research studies. Review is required regardless of source of funds or lack of (source) and regardless of the location of the site at which the research is performed. The Committee on Human Research is authorized by the Dean of the School to perform functions in accordance with the policy and procedures set forth by this Institution and in compliance with the U.S. Code of Federal Regulations Department of Health and Human Services (DHHS), the Office for the Protection from Research Risk (OPRR) Title 45 Part 46 entitled "Protection of Human Subjects." A copy of the DHHS and the OPRR regulations and guidelines may be obtained from the Office for Research Subjects Room 1606 Hygiene. The Committee on Human Research's multiple assurance number issued to the DHHS is IRB 01 M1090 and is effective through July, 1992. A copy of the multiple assurance filed with the DHHS is available in the Office for Research Subjects, Room 1606. 2 (02/92) INTRODUCTION The Committee on Human Research Policy and Procedures Manual (1992) is intended to serve three principal purposes. It documents the philosophy and policies of The Johns Hopkins University School of Hygiene and Public Health regarding the protection of human subjects. It provides instructions for investigators for complying with School and Federal requirements concerning human subjects research. Finally, it serves as a guide for members of the School's Committee on Human Research. While readers are encouraged to become familiar with the entire document, research investigators are directed to Section 2 for basic information concerning this School's requirements. Before any faculty member, staff member or student of the School conducts any kind of research with human subjects - regardless of the source of funding, geographic location, or level of risk - the investigator must complete and submit to the Committee on Human Research: The CHR application form - including research plan and pertinent instruments. Depending on the nature of the study and the level of risk to subjects, the investigators may determine that the research qualifies as "exempt". Research determined to qualify and "exempt" does not require full Committee on Human Research review, however, even in the case of "exempt" research the CHR requires investigators to submit the research application, in triplicate for certification of exempt status before involving human subjects in the research. (See Section 2, Item 3, Page 7, "research Exempted From Full CHR. Review" for complete details.) Studies involving interaction with the Johns Hopkins Hospital patients or staff-, the use of Johns Hopkins medical records; and/or collection of specimens in which there is identifiable linkage to the study must be reviewed by the Joint Committee on Clinical Investigation (JCCI), School of Medicine. The function and review procedures carried out by the members of the Committee on Human Research are addressed in Section 3. Additional information about particular issues such as informed consent or confidentiality is provided in Section 4. This section also includes suggestions for complying with Johns Hopkins University requirements as well as stipulating in more detail the conditions under which certain specific requirements, such as, written documentation of informed consent apply or may be waived.Information concerning the use of special populations (i.e, minors, pregnant women, prisoners, the mentally disabled) is provided in Section 2. 3 DEFINITIONS (as defined in the Federal Regulations 45 CFR 46 issues March 8, 1983) 1. "RESEARCH" means a systematic investigation designed to develop or contribute to generalizable knowledge. Activities which meet this definition constitute "research" for the purposes of these regulations, whether or not they are supported or funded under a program which is considered research for other purposes. For example, some "demonstration" and "service" programs may include research activities. 2. "HUMAN SUBJECT means a living individual about whom an investigator (whether professional or student) conducting research obtains (1) data through intervention or interaction with the individual or (2) identifiable private information. "Intervention" includes both physical procedures by which data are gathered (for example, venipuncture) and manipulations of the subject or the subject's environment that are performed for research purposes. "Interaction" includes communication or interpersonal contact between investigator and subject "Private information" includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording take 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 (i.e, 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 in order for obtaining the information to constitute research involving human subjects. 3. "CHILDREN" are persons who have not attained the legal age for consent to treatment or procedures involved in the research, under the applicable laws of the jurisdiction in which research will be conducted. The age of majority in the State of Maryland is 18 years. 4. "MINIMAL RISK" means that the risks of harm anticipated in the proposed research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. 5. "PREGNANCY" encompasses the period of time from confirmation of implantation (through any of the presumptive signs of pregnancy, such as missed menses, or by medically acceptable pregnancy test), until expulsion or extraction of the fetus. 6. "FETUS" means the product of conception from the time of implantation (as evidenced by any of the presumptive signs of pregnancy, such as missed menses, or by a medically acceptable pregnancy test), until a determination is made, following expulsion or extraction of the fetus that it is viable. 4 7. "VIABLE FETUS" as it pertains to the fetus means being able, after either spontaneous or inducted delivery, to survive (given the benefit of available therapy) to the point of independently maintaining heartbeat and respiration. 8. "NONVIABLE FETUS" means a fetus ex utero which, although living, is not viable, and is an estimated 20 weeks of gestation and a body weight of 500 grams. 9. "DEAD FETUS" means a fetus ex utero which exhibits neither heartbeat, spontaneous movement of voluntary muscles, nor pulsation of the umbilical cord (if still attached). 10. "IN VITRO FERTILIZATION" means any fertilization of human ova which occurs outside the body of a female, either through a mixture of donor sperm and ova or by any other means. 11. "PRISONER" means any individual involuntarily confined or detained in penal institution under a criminal or civil statute; individuals detained in other-facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution; and individuals detained pending arraignment, trial or sentencing. 12. "LEGALLY AUTHORIZED REPRESENTATIVE" means an individual or judicial or other body authorized under applicable law to consent on behalf of a prospective subject to the subject's participation in the procedure(s) involved in the research. 13. "INSTITUTION" means any public or private entity or agency (including federal, state or other agencies). 14. "CERTIFICATION" means the official notification by the institution to the Department in accordance with requirements that a research project or activity involving human subjects has been reviewed and approved by the Institutional Review Board (IRB) in accordance with the approved assurance on file at the Department of Health and Human Services (DHHS Forms 398 and 596). (Certification is required when the research is funded by the Department]. A "Committee on Human Research" (CHR) Application Form is to be used to submit a human subjects protocol for CHR review, and contains pre-printed instructions on submission requirements. (See Appendix A for a sample). 5 (02/92) I. STATEMENT OF GENERAL POLICY OF THE SCHOOL OF HYGIENE AND PUBLIC HEALTH FOR THE PROTECTION OF HUMAN SUBJECTS A. ETHICAL PRINCIPLES The School of Hygiene and Public Health of the Johns Hopkins University is dedicated to the task of protecting and respecting the rights and dignity of all individuals participating in public health, behavioral and biomedical research, and other related activities involving human subjects which are directly or indirectly carried out by the faculty, students, and employees of the School, without regard to sources of funding or geographic location. The School is guided by the basic ethical principle regarding human research subjects as enunciated in the Declaration of Helsinki adopted by the World Medical Assembly, Helsinki Finland, 1964, and amended in Tokyo, Japan,1975. (The Declaration of Helsinki, see Appendix A.) The School also applies the following three basic ethical principles set forth in the Belmont Report "Ethical principles and Guidelines for the Protection of Human Subjects of Research": Respect for Persons - an obligation never to treat a person as a means only; an obligation to respect the autonomy of others; and to protect the interests of persons with diminished autonomy. Beneficence - an obligation to do good and to avoid harm; and an obligation to balance potential benefits and potential harms. Justice - an obligation to treat similar cases in a similar fashion; and an obligation to establish a fair distribution of burdens and benefits. B. INSTITUTIONAL POLICY The Committee on Human Research (formerlv Committee on Human Volunteers), is comprised of qualified and professionally competent individuals representing diverse disciplines and professions, was established 6 (02/92) by the School in 1966, to assure compliance with the ethical principles adopted by the School and with the policy and requirements of the Department of Health and Human Services, as set forth in Public Law 93-348, and Part 46 Title 45, of the Code of Federal Regulations on the Protection of Human Subjects as amended March 8, 1983 and 1991. The Dean of this School has delegated to the Committee on Human Research the authority to review, approve or disapprove, terminate, or require modifications of all research projects and other related activities that involve human subjects. The Committee on Human Research review process will fully adhere to Section 46.111 of 45 CFR, Part 46, Criteria for IRB Approval of Research. For each project, the Committee determines that all the following requirements are satisfied: (1) The research methods are appropriate to the objectives of the research and field of study thereby minimizing risk to subjects; (2) The rights, dignity and welfare of the subjects involved are adequately protected; (3) There has been a careful assessment of inherent and potential risks in comparison to foreseeable benefits to the subject or to society; (4) The subject will be appropriately informed of the purpose and nature of the research activity; (5) Voluntary informed consent will be obtained by methods which are adequate and appropriate; (6) The subject will be apprised of the right to withdraw from participation in the research activity; (7) The subject will be mentally, physically and legally competent to be able to exercise fully the power of choice to participate, or, if the subject is not able to give consent, the consent will be procured from the authorized legal guardian; and (8) Provisions will be taken to protect the privacy of the participants and safeguard the confidentiality of information. The Committee reviews are to be conducted with objectivity and in a manner which will ensure the exercise of independent judgement of the members. Members are to be excluded from reviews of projects and/or activities in 7 (02/92) which they have an active role or which could pose a conflict of interest. The School provides facilities for Committee meetings, and personnel for staffing the Committee. The School encourages continuing constructive communication between the Committee and the principal investigators,project directors, and department chairmen, as a means of protecting the rights of human subjects. The School maintains appropriate and informative records of: Committee reviews of research projects and activities; documentation of informed consent, and other documentation that may pertain to the selection, participation. and protection of subjects; a continuing review to ascertain the status of the project, to obtain assurances that the research does not adversely affect the rights of individual subjects. The Institution has the facilities and professional staff available for emergencycare of subjects who may suffer a physical or other injury as a result of participation in a research activity. Any injury or untoward effect resulting from the subject's participation in the research must be reported immediately to the Committee. This School's policy and procedures apply to all research activities which may involve risks to human subjects. This includes activities which involve intervention or interaction with children and adults, the review of medical records, as well as the use of the fetus, the abortus, and the dead. The use of organs, tissues, body fluids, or graphic written or recorded information, while they present no physical risks to the subjects, could create medical-legal risks, or expose the subject to public embarrassment or humiliation through breach of confidentiality and invasion of privacy. This School's policy and procedures covering the protection of human subjects apply to: the use of students in classroom demonstration or research activities; all cooperative and collaborative research; as well as research conducted in foreign countries; The School periodically determines, through appropriate administrative overview and intercommunication, whether the policies and procedures designed for the protection of human subjects are being effectively applied, and are consistent with its assurance as accepted by the Department of Health and Human Services. C. COMMITTEE MEMBERSHIP The Dean appoints the Committee Chair and its members, for such terms as 8 (02/92) are consistent with prevailing School policies. One year appointments are reviewed annually with a usual time served equivalent to five years. Members of the Committee represent diverse experience int he following areas: Administration; Clinical Medicine; Laboratory and Behavioral Sciences; Epidemiology; Biostatistics; International Health; Health Policy and Management; Maternal and Child Health; Immunology and Infectious Diseases; Environmental Health Science, Community Services and the Law. Student members are candidates for degrees requiring research projects and have been in residence at the School for at least one full year prior to appointment. At least two representatives of the community, including and preferably a member at the clergy, also serve on the Committee. The Committee makes use of consultants from within and outside the University when special expertise is necessary or desirable. For studies involving vulnerable populations, the Committee enlists the assistance of individuals who are advocates for the specific group or groups; D. COMMITTEE STAFF The Director of the Office for Research Subjects also serves as the Administrative Director of the Committee on Human Research and primary staff to the Committee. E. COMMITTEE MEETINGS The Committee on Human Research meets regularly on the first Wednesday of each month. As necessary, the chair may schedule additional meetings on an interim basis. An Executive Subcommittee which includes a rotation of chair,vice-chairs and members meet on an interim as needed basis. A quorum, which is comprised of a majority of the voting members, including at least one member whose primary concerns are in non-scientific areas, must be present for the Committee to transact any business. F. COMMITTTEE RECORDS The Committee maintains complete records of its meetings. A Committee Report is distributed to the Advisory Board each month. The following documents for each research project reviewed by the CHR are kept on file by the Committee: (1) Committee on Human Research application form completed and signed by the principal investigator and co-signed by the department chairman. (Appendix B) (2) A copy of the research plan, including protocol and final survey instrument(s). 9 (3) A Research Plan summarizing specific items in the Research Protocol. (4) A Copy of the Informed Consent Form and/or Disclosure Statement. (5) Recommendations of the primary Committee reviewer. (6) Correspondence between the Committee Chairman and the Principal Investigator. (7) Letters of Agreement or Statements of Approval from cooperating or collaborating institutions. (8) Statement of all Committee on Human Research actions. (9) If international population a cross-translation from English to Native language of consent forms and questionnaires and/or verification of translation from investigator. II. RESPONSIBILITY OF PRINCIPAL INVESTIGATORS AND DEPARTMENT HEADS FOR SUBMITTING A RESEARCH APPLICATION TO THE COMMITTEE ON HUMAN RESEARCH This section provides both basic information and instructions for submitting astandard research proposal requiring Committee on Human Research action; and procedures for processing research applications determined by the investigator to qualify for "exempt" status. Federal regulations do not specify any type of institutional review for exempt research; however, it is the policy of the School that an-investigator must provide the CHR with documents to support the nomination for exempt status, who then certify to be exempt or not. Investigators are expected to self-impose the highest level of ethical principles in all of their research activities (see item C in this section). A. PROCEDURES FOR SUBMITTING NEW APPLICATION Principal investigators and student investigators, in conjunction with their advisors, are responsible for making the initial determination as to whether proposed research will involve human subjects. A human subject is defined in the Federal Regulations as a living individual about whom an investigator (whether professional or student) conducting research obtains: (1) data through intervention or interaction with the individual; or (2) identifiable private information (Refer to Definitions, page iii) 10 Investigators may seek assistance in clarifying the appropriate use of human subjects by communicating with the Office for Research Subjects/Committee on Human Research (955-3193). Before beginning an activity that involves human subjects, the principal investigators, program directors, and student investigators in conjunction with their faculty advisors are required to submit three copies (3) of a completed CHR application (as defined below) to the Committee on Human Research Staff Office, Room 1606 Hygiene, at least three weeks prior to the monthly CHR meeting. (Schedule is available for all departments) Exceptions to this deadline must be in writing, and are presented to the chair for approval to accept late submission. The documents required are: 1. CHR Application Form Each item on this brief checklist (side two of the form; Appendix B)must be answered. Any item which is not applicable should be marked N/A. The application form must be signed by both the principal investigator and the department chair. In the case of student research, the application form must be signed by the faculty advisor, the student, and the department chair. This form is available in the CHR Staff Office, Room 1606 Hygiene. 2. Research Summary Each of the items listed on the reverse side of the CHR Form (Appendix B) should be addressed. The purpose of the Research Plan is to briefly summarize more detailed information in the research protocol. The abstract should be limited to three (3) pages. 3. Research Protocol or Grant Application This documents should clearly describe the details of the study design including specific procedures for safeguarding the rights of human subjects and measures to preserve confidentiality. Do not include budget sheets, appendices, and curriculum vitae. 4. Disclosure Statement and/or Informed Consent Form See Section IV, page 21, Guidelines For Preparing Disclosure/Informed Consent Statement. If the project involves more than minimal risk with respect to possible injury, the subject should be informed that neither The Johns Hopkins Hospital The Johns Hopkins University, nor the Federal Government 11 (02/92) have a program to provide compensation for research subjects who may experience an injury which is not due to the fault of the investigator. Subjects should be advised as to whom they should contact for cassistance in obtaining appropriate medical care after an injury occurs. 5. Other Relevant Documents (as appropriate) It may be necessary to furnish additional documents (as describedbelow) to complete the application if the study involves; (a) questionnaires or personal interviews; (b) personal contact with research subjects in the greater Baltimore Metropolitan area; (c) patients at the Johns Hopkins Hospital; (d) research in a foreign country; or (e) collaboration with other institutions. a. Ouestionnaire or Data Gathering Form A copy of the questionnaire or data gathering form must be submitted for CHR approval prior to conducting personal interviews, telephone interviews, or initiating data gathering by mail. If these documents have not been prepared at the time the application is submitted to the CHR the principal investigator should describe in outline form the areas to be covered in the questionnaire or interview; indicate if the information to be gathered is either sensitive or would constitute any potential invasion of privacy; and provide examples of the type of specific questions to be asked. The investigator should indicate when the documents will be presented to the Committee for review. The data collection instruments must be reviewed and approved by the Committee prior to initiating any field work. b. Research Involving Interviews in the Greater Baltimore Area For any activity in which there will be personal contact with members of the greater Baltimore community, a Field Interview Form (See Appendix D) must be completed. This form may be obtained from the Staff Office, Room 1606. To dispel any fear of deception within the community and at the same time provide appropriate credentials for Johns Hopkins University employees, all Johns Hopkins Medical Institutions (JHMI) field interviewers are requested to carry anauthorized identification card to validate their credentials. A 12 copy of the disclosure statement or consent statement should be left with the respondent. C. Research Involving Drugs. Radiation, Pregnant Women, Fetal Tissue or Biohazardous Agents For studies involving any of the above special areas,additional pertinent information will be required and will be forwarded to the JCCI who will direct these documents to the appropriate hospital committees for review and advice. Investigators should provide the specific documents described below if the research involves the following special areas: Research Area Exposure of subjects to ionizing radiation (X-rays, radioisotopes) Use of infectious or biohazardous agents Research on fetal tissue or pregnant women (this includes clinical procedures and questionnaires) Use of an investigational new drugs TM) Documents to Append to CHR Application Radiation Control Unit Form 5 (available in CHR office) JCCI Policy on Radiation Risks Detail of containment procedures Maternal Care and Fetal Tissue Committee form (available in CHR office) Investigational Drug Data Sheet Investigators who are involved in studying new drugs should immediately report drug reactions to the Committee on Human Research no matter how insignificant the side effect may appear. The liaison member of the Pharmacy and Therapeutic Committee on the JCCI will be contacted promptly to seek consultations regarding further procedures. d. International Research Studies Investigators planning to carry out research in a foreign country must provide the Committee on Human Research with appropriate documentation certifying that approval or authorization to conduct the study has been obtained from the Minister of Health or an appropriate institutional authority in the country in which the research is to be conducted. e. Collaborative Institutional Studies If the research is to be conducted in collaboration with other 13 (02/92) institutions, the investigator should include with research application a section identifying the institutions and the procedures underway for receiving the approval of their institutional review board(s). Letters of approval as well as communications requesting modifications from collaborating institutions must be filed with the CHR. B. Research Involving Johns Hopkins Hospital Patients: Studies involving the clinical management of patients, review of medical records, interviewing or surveying patients, staff and/or employees of the Johns Hopkins Hospital,must be reviewed and approved by the Joint Committee on Clinical Investigation (JCCI), which serves as the Hospital and Medical School institutional review board. If the Hospital serves as the main study site, do not complete the CHR Application Form, but complete and submit the JCCI Research Proposal Notification Form in duplicate to the CHR The CHR staff will coordinate and facilitate the review. Since the JCCI will be reviewer of the research involving the study population, final approval is determined by the JCCI action. (Copies of the JCCI RPN are available in the CHR Staff Office.) A corresponding file will be maintained on School of Hygiene faculty and students. C. New Applications Requiring Special CHR Action 1. EMERGENCY REVIEW AND APPROVAL: Committee approval of a protocol requested to be revised. a. Type of Activities Which Qualify: (1) Studies funded by the Department of Health and Human Services may only be approved on an emergency basis if the activity is connected with emergency medical care or if the study qualifies for expedited review. (2) AIDS related research needing IRB review at time of application. (3) Other studies which qulify for review between regularly scheduled meetings Usually pose no more than minimal risk to the subjects and involve short-term studies conducted in conjunction with course work. A request for emergency approval of a study will be considered by the chair of the CHR on a case-by-case basis. b. The Following Documents Should be Submitted: 14 (02/92) (1) A written request for emergency action and a statement explaining the exceptional circumstances and how the research would be impeded without interim action. (2) Three copies of the completed CHR application and all accompanying documents. c. Committee Action: (1) The Chair appoints a subcommittee or assigns review to the Executive Subcommittee to review the proposal and requests that the recommendations be reported back to the chair within one week. (2) Interim approval is contingent upon the subcommittee's unanimous agreement that the benefits outweigh the risks. (3) If the subcommittee approves the research, the Chair notifies the investigator of the Committee's action. (4) This action is reported at the next scheduled Committee meeting, at which time final approval is confirmed. (5) If the subcommittee notes any objections to the study procedures, the chair notifies the investigator in writing, outlining the points of concern. Final action is deferred for further discussion at the next Committee meeting. 2. Expedited Review a. Federal Regulations Federal regulations allow for research activities involving no more than minimal risk to the study population to be handled by the Committee on Human Research through an expedited review and action process. This regulation does not alter the Committee's policy of requiring the investigators to follow the established procedures for completing the CHR Form and submitting the protocol and necessary documents to the Committee for review. The designation "minimal risk" applies where the "risks of harm anticipated in the proposed research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests". 15 (02/92) b. Policy of the Committee on Human Research Research which meets the criteria for minimal risk; reflects a minor change in a previously approved study; is a grant proposal lacking definite plans for involving human subjects and is being submitted to a granting agency for funding; or is a student course activity using human subjects outside of the classroom will qualify for CHR expedited action. This is generally limited to those studies in which no individual can be identified from the information collected and/or the data contain no sensitive information. To expedite Committee action on research which qualifies for this type of action, the Chair of the CHR delegates to a member of the Committee and the Staff Director the responsibility to review the application and recommend a course of action. In reviewing the research the reviewer may exercise all of the authorities of IRB, except to disapprove the research. If the research proposal is acceptable, interim approval is forwarded to the investigator. Each month, the CHR Agenda will include a list of studies handled by expedited review and backup information for further discussion if necessary. (1) The following categories are examples of the kinds of research which may qualify for expedited review: (a) The study of existing data, documents,records,and specimens (b) Student course activities conducted outside the classroom (c) Collection of blood samples by venipuncture (d) Collection of hair and nail clippings, excreta or secretions (e) Studies on the behavior of groups (f) Research on drugs or devices for which IND exemption is not required. (2) The following documents should be submitted: (a) For umbrella grants in which no specific projects have been defined: 16 (i) Two(2)copies of the grant application submitted to the funding agency.(DO NOT INCLUDE budget information, biographical sketch or bibliography.) (ii) Three(3)copies of the CHR Form. Note those items which are not applicable. The Abstract Summary is not necessary for these applications inasmuch as the details are incomplete. (iii)Written assurance that specific projects involving human subjects will not be initiated without the Committee's review and approval of the other necessary documents. (b) For specific projects which involve no risk or minimal risk, Three(3)copies of the complete CHR Form, including the research plan, protocol and accompanying documents. (c) For student course activities using human subjects outside of the classroom: (i) The instructor should anticipate the type of studies the class plans to conduct and provide a listing and description of the class projects along with the names of students associated with the project. (ii) The instructor should provide assurance that the projects involve no more than minimal risk; that the students have been carefully informed about the procedures for protecting the rights of research subjects, especially concerning securing informed consent, safeguarding privacy and maintaining confidentiality. Copies of survey instruments must be submitted for review. 17 (02/92) 3. Research Exempted From Full CHR Review: a. Federal Regulations Federal regulations (effective March 1983) permit universities to exempt from institutional review certain categories of research in which the only involvement of human subjects will be in one or more of the following categories: (1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special educational instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula,or classroom management methods. (2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) Information obtained is recorded in such manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonable place the subjects at risk of criminal or civil liability or be damaging to the subjects' financial standing, employability, or reputation. (3) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if; (i) The human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. (4) Research, involving the collection or study of existing data, documents,records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified directly or through identifiers linked to the subjects. (5) Research and demonstration projects which are conducted by or subject to the approval of department or agency heads, and which are designed to study, evaluate,or otherwise examine: (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits 18 (02/92) or services under those programs. (6) Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contaminant at or below the level found to be safe, by the Food and Drug Administration or approved by the Environmental ProtectionAgency or the Food Safety and Inspection Service of the U.S. Department of Agriculture. b. Policy of the Committee on Human Research Although research determined to qualify as "exempt" does not require full CHR review, the CHR requires investigators to submit the research application in triplicate for expedited action before involving human subjects in the research. Investigators are required to submit the CHR Form, the protocol or the PHS 398 Form, a research summary and a disclosure/informed consent form or a statement explaining why consent will not be obtained (if applicable). PLEASE NOTE: Studies involving interaction with the Johns Hopkins Hospital patients or staff; the use of Johns Hopkins' medical records; and/or collection of specimens in which. there is identifiable linkage to the subject must be reviewed by the JCCI The CHR Staff Office will process the application. Survey and inter-view protocols that involve patients or staff of the Johns Hopkins Hospital are not exempt from JCCI review. The following delineates the investigator's responsibility for processing research submitted as exempt from CHR review: (1) Make the initial determination that the research is exempt; (2) Complete the CHR Form checking the appropriate items indicating that the research qualifies as exempt and addressing the elements for protecting human subjects; (3) Have the CHR Form reviewed and cosigned by the department chair who should affirm that the investigator has made the correct determination (to the best of their knowledge); (4) Provide the CHR with the Protocol and a Research Plan Summary of the research; and 19 (02/92) (5) Provide the CHR with a copy of the disclosure/informed consent statement, or a statement explaining why consent will not be obtained. There will be caseS of exempt research where the informed consent obligation may be justifiably waived, for example, observational studies of anonymous individuals in public settings or record review-studies where no identifiers are collected. The decision not to obtain consent is, in the case of exempt research, up to the investigator, but must have concurrence of the CHR. 4. Research Involving Special Study Populations: MINORS a. Federal Regulations In June,1983, the Department of Health and Human Services (DHHS) finalized new regulations entitled "Additional Protection for Children Involved as Subjects of Research". These regulations are designated as 45 CFR 46, Subpart D. Definitions: "Children" are persons who have not attained the legal age for consent to Treatments or procedures involved in the research, under the applicable laws of the jurisdiction in which research will be conducted. The age of majority in the State of Maryland is 18 years. "Assent" means the child's affirmative agreement to participate in research. Mere failure to object, absent affirmative agreement, should not be construed as assent. "Parent" means the child's biological or adoptive parent. "Guardian" means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care. b. Policy of the Committee on Human Research The Committee on Human Research will review applications involving minors to determine whether the research is in compliance with the federal requirements. The CHRs basic review procedures will continue unchanged for all protocols, but investigators should be aware of additional elements of 20 (02/92) review that will be used to comply with the federal regulations applicable to research involving children. Copies of these regulations are located in the CHR Staff Office and in the Interdepartmental Library. Investigators should address the following issues in the CHR application to justify the use of children as research subjects. (1) Where relevant, studies have been conducted first on animals and adult humans, then on older children prior to involving infants. (2) Risks (a) If the research represents more than minimal risk, but with the prospect of direct benefit to the individual subjects, the risk section should address the following criteria: - the risk of participation in the protocol must be justified by the anticipated benefit to the subjects; - the relation of the anticipated benefit to the risk must be at least as favorable to the subjects as that presented by available alternative approaches; - adequate provision must be made for soliciting the assent of the children as well as consent of their parent(s) or guardian(s). (b) If the research presents more than minimal risk and no prospect of direct benefit to the individual subjects, but is likely to yield generalizable knowledge about the subject's disorder or condition then the risk section should address the following criteria: - the risk should be a minor increase over minimal risk; - the intervention or procedure should present experiences to the children that are reasonably commensurate with those in their actual or expected medical, psychological or social situation; - the research is likely to yield generalizable knowledge about the subject's disorder which is of vital importance for the understanding or amelioration of the subject's disorder or condition; - an adequate provision will be made for soliciting the assent of the children and the consent of their parent(s) 21 (02/92) or guardian(s). (3) Consent/Assent The Committee recognizes that the formulation of a consent form for parents and an assent form for the child is difficult. We suggest different approaches for each of four age ranges. a) Children younger than 5 vears: A simple oral explanation of the study should be offered to the child before study-related procedures are conducted. (For a blood drawing study, for example: "We have to draw some blood for______. That means you will feel a little needle stick. It will only hurt for a minute. Your mom (or dad) will be with you the whole time." b) Children between the ages of 5 and 12 years: Informed voluntary assent should be obtained without pressure from parents or investigators. The application should include an examples of the explanation to be offered to the child. Assent from the child should be solicited in the presence of a parent, and the consent form should include the following statement from the investigator: "This project has been explained to my child in my presence, in language he/she can understand. He/she has been encouraged to ask questions, both now and in the future, about the research study." After the child has voiced assent, the parent and investigator (and witness, if appropriate) should sign the consent form. c) Children between the ages of 12 and 16 years: Investigators may choose to handle the consent/assent requirements for this group in one of two ways. They may either submit a consent form that is written at a level simple enough for both parent and child to read meaningfully (i.e, about a fifth grade reading level) or they may choose to submit a consent form for the parents and a separate assent form for the child to read and sign. If a consent form is designated for both the parent and a child, the forms should be signed by each after the study has been explained. An assent form should be written as simple as possible and 22 (02/92) cover the following points: - what the study is about - why he/she qualifies for the study - what procedures will be done - potential benefit - potential risks - an assurance that he/she will be treated the same whether or not he/she may withdraw from the study after discussing with his/her parents. The assent forms should contain signature lines for the child and the investigator. d) Children between the ages of 16 and 18 years; A consent form written in language that is easily understandable for both the parents and the child is sufficient for this group. A separate usent form need not be used. The parent and child must sign the consent form. The only exception would be in the case of an emancipated minor who would not require parental cosignature before agreeing to join the study. e) Studies involving children of ALL ages: If studies involve children of all ages, a consent/assent form should be written as in paragraph 3 of these guidelines with a final statement from paragraph 2. (4) Wards of the State The use of children who are wards of the state or any other agency, institution or entity as subjects of research may be approved if such research is related to their status as wards; or is conducted via settings in which the majority of children involved as subjects are not wards. The CHR may appoint an advocate who is not associated with the research, investigator(s) or guardian in any way, and who agrees to, and is able to act in the best interests of the child for the duration of the child's participation in the research. PRISONERS 23 (02/92) a. Federal Regulations Since the right to freely refuse to participate in research projects is extremely difficult to assure in a prison setting, special attention has been given to prisoners as study subjects. A prisoner is defined as "any individual involuntarily confined or detained in a penal institution. The term is intended to encompass individuals sentenced to such an institution under as criminal or civil statute, individuals detained in other facilities by virtue of statutes or commitment procedures which provide alternatives to criminal prosecution or incarceration in a penal institution and individuals detained pending arraignment, trial, or sentencing". The amended Part 46 of CFR 45 Subpart C, Section 46.306 states that research supported by DHHS may involve prisoners only if an institutional review board has approved the research and the research involves one of the following: (1) Study of the possible causes, effects, and processes of incarceration and of criminal behavior provided that the study presents no more thanminimal risk and no more than inconvenience to the subjects. (2) Study of prisons as institutional structures or of as incarcerated persons, provided that the study presents nor more than minimal risk and no more than inconvenience to the subjects. (3) Research on conditions particularly effecting prisoners as a class (for example, vaccine trials and other research on hepatitis which is more prevalent in prison than elsewhere; and research on social and psychological problems such as alcoholism, drug addiction and sexual assaults) provided that the study may proceed only after the Secretary has consulted with appropriate experts including experts in penology medicine and ethics, and published notice in the Federal Register of his intent to approve such research. (4) Research on practices, both innovative and accepted, which have the intent and reasonable probability of improving the health or well beingof the subject. Prisoners may not be assigned to controlled studies if they will not derive benefit from the research rights of human subjects. These may involve modifications in the research design; the type of study subjects; or procedures altering the risk-benefit balance. The Committee reviews the research proposal for the risk-benefit balance; procedures which are consistent with sound research design; 24 (02/92) the selection of subjects; the adequacy of procedures for obtaining and documenting informed consent; and procedures for protecting privacy and safeguarding confidentiality. Also, if an institutional review board is to consider a project involving prisoners, Sections 46.304 and 46.305 state that a least one prisoner or prisoner advocate must serve on the institutional review board. b. Policy of the Committee on Human Research on a case-by-case basis. Pregnant Women, Fetuses, Human In Vitro Fertilization a. Federal Regulations Sections 46.201 through 46.209 of 45 CFR 46 are concerned with research on pregnant women, fetuses, and human in vitro fertilization. In order for such research to take place under DHHS sponsorship, it must be approved by an Ethical Advisory Board established by the Secretary. The purpose of the activity must meet the health needs of the mother or the particular fetus, the risk to the fetus being minimal and the least possible for achieving the objectives of the activity. The responsibility of the institutional review board is todetermine that: (1) Appropriate studies on animals and nonpregnant individuals have been completed; (2) Adequate consideration has been given to the selection of potential subjects; and adequate provision has been made by the applicant for monitoring the informed consent process; (3) Except where the purpose of the activity is to meet the health needs of the mother or the fetus, the risk to the fetus is minimal; and in all cases is the least possible risk for achieving the objectives of the activity; (4) An activity permitted under this section may be conducted only if the mother and father are legally competent and have given their informed consent, except that the father's informed consent need not be secured:(1) if the purpose is to meet the health needs of the mother,(2) his 25 (02/92) identity or whereabouts cannot reasonably be ascertained; (3) he is not reasonably available; or(4) the pregnancy resulted from rape. (5) Individuals engaged in the activity will have no part in the timing, method and procedures used to terminate the pregnancy, anddetermining the viability of the fetus; (6) No procedural changes will be introduced which may cause greater than minimal risk to the fetus or the pregnant woman; (7) No monetary inducements may be used to terminate the pregnancy, (8) Activities directed towards fetuses in utero, ex utero, including nonviable fetuses, must be aimed at the development of important biomedical knowledge which cannot be obtained by other means b. Policy of the Committee on Human Research Activities involving pregnant women, fetal tissue, or abortus require the approval of The Johns Hopkins Maternal Care and Fetal Research Committee and are forwarded via JCCI, who facilitate their subcommittee. Institutionalized as Mentally Disabled a. Federal Regulations DHHS is currently considering the recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research regarding the use of institutionalized or the mentally disabled subjects. Each proposal will be considered on a case-by-case basis, using the National Commission's recommendations as guidelines. Currently guidelines on competency developed by JCCI at JHMI are under review by the CHR. Students as Research Subjects a. Student Participation in Classroom Demonstration Activities (Non-Research) (1) The Committee on Human Research should be notified of any training or research program which uses students as subjects for classroom orlaboratory exercises. (2) The course instructor should describe the nature of the student's participation; the presence or absence of risks; and the assurance that 26 (02/92) procedures involving risk are carried out under the supervision of senior faculty personnel. (3) Participation as a human subject may not be required either explicitly or implicitly as a term or condition of the student's academic enrollment or progress. b. Recruitment of Students as Subjects for Specific Research Projects The consent form given to the student should state that participation in the research activity is not a condition of their academic enrollment, grades or employment. To seek relief from participating in a classroom demonstration project or a research project, the student may contact the Associate Dean for Student Affairs. Self-Experimentation Faculty and staff members who wish to become involved as experimental subjects in the development of their research should consider themselves to be "human subjects", and the Committee requests notification of this intent before the experiment is initiated. There are two reasons for the need to submit an application for self-experimentation protocols: (1) To protect the prospective subject from taking unwarranted risks in the excitement of generating new knowledge. Under these circumstances investigators are enthused about the prospect of new knowledge, and concern for any associated risk may be minimized or escape attention. (2) To protect the process of human investigation in an era when the process has articulate critics. While the recommendation for review may be viewed as a limitation of personal freedom, it is the price one must pay to protect clinical investigation. If there were an accident leading to death or a permanent handicap, a number of issues regarding insurance coverage, benefits, etc.would have to be addressed. The DHHS Office of the Protection from Research Risks has stated "... although the human subject regulations do not specifically address this issue, it is the intent of the Department that the regulations apply to self experimentation. Accordingly, unless the research is otherwise exempt, such research should receive IRB review and approval prior to commencing". The Committee concurs with this interpretation. D. CHR Procedures for Processing Applications (See Section III page 14) E. General Assurance Statement of Compliance for Federal Grants and Contracts (PHS 398 and DHHS Form 596) 27 Federal regulations concerning the protection of human subjects require that each research grant or contract proposal involving human subjects (or planned use of human subjects) submitted to a federal funding agency must indicate on the PHS 398 application form, at the time of submission, the date of IRB approval If the grant is submitted to the federal agency as "pending' approval the principal investigator is responsible for obtaining CHR approval within 60 days following the initial submission date and completing the Department of Health and Human Services (HHS) Form 596 (Appendix F) with the requested information. These forms are obtained and processed through the Sponsored Projects Office. - Both the Form 398 and 596 should include the School of Hygiene and Public Health: General Assurance number (MlO9O-Ol); the date the Committeeapproved the study-, and the Dean's signature. Follow-up submission of the Form HHS-596 (Protection of Human Subjects Assurance/Certification/Declaration) is still required for all research involving human subjects (as defined in 45 CFR 46), whether exempt or not. However, no response need be made to item number 4 on the Form HHS-596-when an exemption is claimed. When an exemption to the human subjects regulations is claimed, the application or proposal must indicate the exemption #. Insert the identification number(s) of exemptions(s) claimed by using the numbers in 45 CFR 46.101 (b) 1 through 6. F. Proposed Modifications of the Original Protocol Principal investigators have a responsibility to notify and to seek CHR approval for any substantive changes in the study (as it was approved) that may affect the interests or rights of human subjects. These may involve modifications in the research design; the type of study subjects; or the procedures altering the risk-benefit balance. 1. Renewal Applications All non-exempt research projects and other activities involving human subjects are reviewed annually by the CHR. The principal investigator must complete the Annual Review Notice, which is mailed to the investigator automatically by the CHR staff six weeks in advance of the anniversary date of original approval. The purpose of this notice is to inform the Committee of the status of the study. (see Appendix E, Annual Renewal Notice.) If there are no changes in the status of the study as described in the original application, the study is approved for another year. For studies still collecting data after three years, the investigator must furnish the Committee with a report summarizing the activities and experience with 28 (02/92) human subjects to date. If a completed Annual Renewal Notice is not returned to the Staff Office within sixty (60) days of the date it is to be reviewed by the Committee, the principal investigator and the department chair will be sent a final notice stating that approval of the project will be withdrawn if the signed form is not returned within the next thirty (30) days. At the end of that period, the Business Office will be sent a formal notice indicating that the CHR approval has been withdrawn and that funding of the project must be terminated immediately. 2. New Information Conceming Effects on Human Subjects The principal investigator has the responsibility to promptly report to the Committee on Human Research and to the Office for Protection from Research Risks any new information or unanticipated problems involving possible risks to human subjects or others. In addition, the-Committee may request status reports on a more frequent basis whenever this is indicated by the nature of the study and/or the degree of apparent risk to the study population. Such periodic reports are reviewed by the full Committee to determine whether further action might be appropriate. The institution Will notify DHHS of any problems or serious noncompliance associated with research funded by the department 3. Disposition of the Data for Inactive Studies When the principal investigator declares a study inactive, plans for the disposition of the data must be furnished to the Committee. The Committee will approve the long-term retention of research records with personal identifiers only when it has been convinced of the necessity of such an exception to normal procedures. In requesting approval for retaining the records beyond the completion of a research study, the investigator should provide the Committee with a separate document outlining what use will be made of the records, an approximate length of time the records are to be retained and an evaluation of the risks and benefits related to long-term retention. If possibility of follow-up is anticipated, the future use of the records should be consistent with the original purposes for which the data were collected. AR precautions should be taken to avoid using the research records for unrelated purposes. The principal investigator should provide a separate statement addressing the 29 (02/92) accrual process and procedures for safeguarding the confidentiality of information. When research records with personal identifiers are to be retained for an extended period of time after completion of the study, the principal investigator has the obligation to place the records in a secured University depository. At this time, the principal investigator's responsibility for the records is terminated. the responsibility for maintaining the custody of research records will be shared between the administration and the department having primary responsibility for the study. It is usually not appropriate for the principal investigator to assume responsibility for safeguarding the security of research records with personal identifiers for extended periods of time beyond the actual final completion date of the study and publication of the study results. G. Subpoena of Research Records If a subpoena for research files is served on or received by an individual investigator, either on his/her own behalf or as an agent of the University,the General Counsel of the University should be contacted immediately for guidance and legal representation. Documents and files should not be surrendered without prior counsel and advice of the University Council Researchers who become expert witnesses in cases where identiffable data is at risk of subpoena are requested to notify the Committee on Human Research as soon as they agree to testify. The Committee may determine that the methods for protecting confidentiality have been adhered to and are adequate. Questions concerning Committee on Human Research procedures should be directed to the Staff Office, Room 1606 Hygiene, extension 5-3193. III. Procedures for Committee Review of Research Proposals Involving Human Subjects This section provides a description of the functions and operational procedures of the Committee on Human Research and outlines the responsibility of the members of the Committee. A. General Information 1. Schedule of Meetings The Committee convenes in the Board Room regularly on the fist Wednesday of each month. 2. Distribution of Materials to Members 30 (02/92) At least five (5) days prior to each monthly meeting, the following material is distributed: a. Report of the previous meeting. b. The Agenda outlining the items which require Committee consideration which includes a list of the following: (1) New Applications; (2) Pending Applications; (3) Applications previously approved with a change in the protocol; (4) Informational listing of exempt research; (5) Annual renewals of previously approved protocols; and (6) Discussion items (7) CHR Activity Report summarizing number of reviews (8) Listing of Handouts C. CHR Form for each new application, along with accompanying: (1) Research Plan and Summary; (2) Informed Consent Statement; (3) Survey Instrument. 3. Voting by the Committee a. All members of the Committee, including students, have full voting rights and their presence counts toward a quorum. A quorum, consisting of a majority of all Committee members,must be present at any meeting in which official business is conducted. b. Final action on an application requires the concurring vote of 31 (02/92) the majority of members present Proxy votes from members not present are not accepted. C. No member of the Committee may vote on any application or activity for which he or she has a professional responsibility. B. Review of New Applications 1. Staff Responsibilities a. Standard Research Proposals The research proposal is reviewed by the CHR staff for completeness. If an application is incomplete, the staff will return the proposal to the principal investigator with a notation indicating the reasons it is unacceptable. The CHR staff is available to provide assistance in clarifing policies and procedures. One or more Committee members are selected to review and conduct an in-depth evaluation of the research application. A course of actionis recommended to the full Committee at the regular monthly meeting. b. Exempt Research A research application submitted as "exempt" will be screened and passed on to a single reviewer to judge whether the research qualifies for the Federal "exempt" status. If the reviewer on examining the documents determines that the research meets the criteria for "exempt" status and the CHR chair concurs, the research would be esignated exempt from full committee review. If the reviewer does not "judge" that the research meets these criteria, the application will be processed for review by the full committee. C. Expedited Research Umbrella Grant proposals (training, program and center grants lacking definite plans to involve human subjects), course activities studies which are of minimal risk of harm to human subjects, revisions or requests for amendments to previously approved protocols will be processed for expedited CHR action by the staff A subcommittee of the Committee appointed by the chair will review the research and initiate action. If the subcommittee is not in full accord, the research plans will be forwarded to the full Committee. 32 (02/92) 2. Standard Review Requiring Full Committee Approval The Committee member(s) who has the responsibility for an in-depth assessment of the research reviews the application includingthe protocol,research plan and accompanying documents. Based on the following criteria,the Committee reviewer(s) shall determine all the requirementsare satisfied: a. Risks to subjects are minimized by using procedures which are consistent with sound research design and which do not unnecessarily expose subjects to risk; and whenever appropriate, by using procedures already being performed on the subjects for diagnostic or treatment purposes. b. Risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects; and the importance of the knowledge that may reasonably be expected to result. In evaluating risks and benefits, the CHR should consider only those risks and benefits, the CHR should consider only those risks and benefits that may result from research. The CHR should not consider long-range effect of applying knowledge gained in the research. C. Selection of the subject is equitable. In making this assessment, the CHR should take into account the purposes of the research and the setting in which the research will be conducted. d. Informed consent will be sought from each prospective subject or the subject's legally authorized representative, in accordance with CHR policy. e. Informed consent will be appropriately documented, in accordance with and to the extent required by CHR policy. f. Where appropriate, the research plan makes adequate provision for monitoring the data collected to insure the safety of subjects. g. Where appropriate, there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data. h. Where some or all of the subjects are likely to be vulnerable to coercion or undue influence, such as students, persons with acute or severe physical or mental illnesses, or persons who are economically or educationally disadvantaged, appropriate additional safeguards have been included in the study to protect the rights and welfare of the subjects. 3 The Reviewer's Comment Form (Appendix G) is then completed by the primary reviewer(s) and returned to the staff office. This will include a written statement commenting on the research and a recommendation for specific action by the Committee. The action must be one of the following: a. Approval of the protocol as submitted. No further submission required. b. Approve protocol. Research instruments to be reviewed by the Committee prior to initiating direct contact with the subjects. C. Defer action: (1) Conditional approval contingent on the following minor revisions (to be specified). If the revisions are accepted, the status of the application will be changed to a or b(above) as appropriate. (2) Require significant modification of the protocol before approval. (3) Request investigator to discuss problems with Committee or with designated subcommittee. d. Reject the protocol (with reasons specified). At the monthly Committee meeting, the comments are discussed in full Committee and a determination is made if the application complies with each of the Committee on Human Research's requirements. A vote by the Committee determines the final recommendation on the research. The reviewer's report and Committee suggestions are made a part of the record. Modifications suggested as "optional" by either the reviewer or other Committee members will be forwarded to the investigator for infomation only at the time of official notification of Committee action. 3. Emergency Review and Approval Under special circumstances the Committee will comply with an investigator's request to review and approve a research study between regularly scheduled meetings. Federal Regulations do not provide for research studies to be given emergency approval unless the activity involves emergency medical care. a. Emergency studies to be undertaken in a foreign country or student short-term research activities are examples of the studies which may 34 (02/92) qualify for interim approval prior to a formal review by the full Committee. b. Procedures for Emergency Action are as Follows: (1) The Staff office will conduct the same review process as outlined under Review of New Applications. (2) Depending on the nature of the study and the risk/benefit balance, a subcommittee of no less than five (5) members,but possible the entire Committee, will review the application and complete a Reviewer's Comment Form. (3) If the subcommittee is in agreement that the study satisfies the guidelines of the Committee, the Chair will issue approval (4) Final approval is dependent upon the unanimous agreement of the subcommittee. (5) The Chair will notify the principal investigator promptly of the subcommittee action. (6) Interim approvals are brought before the full Committee at thenext scheduled meeting for comment and confirmation. (7) If the subcommittee is not unanimous in approving the study, the staff notifies the principal investigator immediately about the issues raised. Copies of all correspondence relevant to the study are furnished to the subcommittee. If the subcommittee cannot reach an unanimous decision of approval prior to the next monthly meeting, the protocol refers to the regular procedure for review of new applications. 4. Expedited Review Research activities which may qualified for expedited review and approval must involve no more than minimal risk of harm to human subjects and must be on the list of categories approved by the Secretary of DHHS for expedited review process. The designation "minimal risk" applies where the "risks of harm anticipated in the research are not greater, considering probability and magnitude, than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests". 35 (02/92) a. Research Which Qualifies for Expedited Action If the protocol meets the criteria for minimal risk and is included on the list of categories approved by the Secretary for expedited review process; or if it reflects only a minor change in a previously approved study; or if it is a grant proposal lacking definite plans for involving human subjects at the time of submission to a granting agency; or if it is a course activity not funded by DHHS, it will qualify for CHR expedited action. Investigators are required to follow the established procedures for completing the CHR Form and submitting the protocols and the documents to the Committee. The Following categories are authorized under Section 46.110 of 45 CFR Part 46 for expedited review process: (1) Collection of: hair and nail clippings, in a nondisfiguring manner, deciduous teeth; and permanent teeth if patient care indicates a need for extraction. (2) Collection of excreta and external secretions including sweat, uncannulated saliva, placenta removed at delivery, and amniotic fluid at the time of rupture of the membrane prior to or during labor. (3) Recording of data from subjects 18 years of age or older using non-invasive procedures routinely employed in clinical practice. This includes the use of physical sensors that are applied either to the surface of the body or at a distance and do not involve input of matter or significant amounts of energy into the subject or an invasion of the subject's privacy. It also includes such procedures as weighing, testing sensory electrocardiography, electroencephalography, thermography, detection of naturally occurring radioactivity, diagnostic echography, and electroretinography. It does not include exposure to electromagnetic radiation outside the visible range (for example, x-rays, microwaves). (4) Collection of blood samples by venipuncture, in amounts not exceeding 450 milliliters in an eight week period and no more often than two times per week, from subjects 18 years of age or older and who are in good health and not pregnant. (5) Collection of both supra- and subgingival dental plaque and calculus, provided the procedure is not more invasive than 36 (02/92) routine prophylactic scaling of the teeth and the process is accomplished in accordance with acceptance prophylactic techniques. (6) Voice recordings made for research purposes such as investigations of speech defects. (7) Moderate exercise by healthy volunteers. (8) The study of existing data, documents, records, pathological specimens, or diagnostic specimens. (9) Research on individual or group behavior or characteristics of individuals, such as studies of perception, cognition, game theory, or test development, where the investigator does not manipulate subjects' behavior and the research will not involve stress to subjects. (10) Research on drugs or devices for which an investigational new drug exemption or an investigational device exemption is not required. b. Procedures for Committee Approval The CHR Director will review the research proposal to determine if the study constitutes minimal risk of harm to human subject. A subcommittee of the CHR will subsequently review the application and recommend expedited approval. (1) Umbrella Grants in which no specific projects involving human subjects have been defined. Committee approval is with the understanding and assurance that the principal investigator will submit a full protocol for each specific project which involves human subjects for Committee review and approval prior to initiating the study. (2) Student Course Activities using human subjects outside of the class room. If after reviewing the instructor's plans for the type of studies the class will conduct and the description of the class projects, the subcommittee is of the opinion that the activities constitute no risk or minimal risk, approval will be expedited. 37 (02/92) C. Full Committee Review All studies which have received expedited Committee approval Will be brought before the full Committee for informational purposes at the next scheduled meeting. The Committee reserves the right to make the final determination concerning whether research falls under this category; however, this is generally limited to those studies in which no individual can be identified from the information collected and/or thedata contain no sensitive information. 5. Research Exempted From Committee (1) Research conducted in established or commonly accepted educational settings, involving normal educational practices, such as (i) research on regular and special educational instructional strategies, or (ii) research on the effectiveness of or the comparison among instructional techniques, curricula, or classroom management methods. (2) Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures or observation of public behavior, unless: (i) Information obtained is recorded in such manner that human subjects can be identified, directly or through identifiers linked to the subjects; and (ii) any disclosure of the human subjects' responses outside the research could reasonable place the subjects at risk of or civil liability or be damaging to the subjects' financial standing, employability, or reputation. (3) Research involving the use of educational tests (cognitive, Diagnostic, aptitude, achievement), survev procedures, interview procedures, or observation of public behavior that is not exempt under paragraph (b)(2) of this section, if.(i) The human subjects are elected or appointed public officials or candidates for public office; or (ii) federal statute(s) require(s) without exception that the confidentiality of the personally identifiable information will be maintained throughout the research and thereafter. (4) Research, involving the collection or study of existing data,documents, records, pathological specimens, or diagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects. (5) Research and demonstration projects which are conducted by 38 (02/92) or subject to the approval of department or agency heads, and which are designed to study, evaluate, or otherwise examine: (i) Public benefit or service programs; (ii) procedures for obtaining benefits or services under those programs; (iii) possible changes in or alternatives to those programs or procedures; or (iv) possible changes in methods or levels of payment for benefits or services under those programs. (6) Taste and food quality evaluation and consumer acceptance studies, (i) if wholesome foods without additives are consumed or (ii) if a food is consumed that contains a food ingredient at or below the level and for a use found to be safe, or agricultural chemical or environmental contamination at or below the level found to be safe, by the Food and Drug Administration or approved by the Envirommental Protection Agency or the Food Safety and Inspection Service of the U.S. Department of Agriculture. b. Policy of the Committee on Human Research (1) The Committee on Human Research permits a category of exempt research but requires the investigator to make the determination and submit it to the CHR for expedited action. (2) Researchers are required to: (a) Make the initial determination that the research is exempt; (b) Complete the CHR Form checking the appropriate items indicating that the research qualifies as exempt and addressing the elements for protecting human subjects; (c) Have the CHR Form reviewed and cosigned by the department chair who should affirm that the investigator has made the correct determination; (d) Provide the CHR with a protocol (or research design as submitted on PHS 398 Form), an abstract summary of the research; and (e) Provide the CHR with a copy of the disclosure/informed consent statement or a 39 (02/92) statement explaining why consent will not be obtained. It should be emphasized that it is the position of the CHR that exempting research from CHR review does not exempt investigators from the standard obligations of research ethics, including the obligation to obtain informed consent. there will however be cases of exempt research where the informed consent obligation may be justifably waived, for example, observational studies of anonymous individuals in public settings or record review studies where no identifiers are collected the decision not to obtain consent is, in the case of exempt research, up to the investigator. (3) Each member of the Committee will be expected to bea liaison with his/her respective department and serve as a resource person to study/faculty investigators seeking clarification of the CHR policy and procedures. (4) The staff response resopnsibilities are outlined an page 14, Section Item 1. Studies involving the Johns Hopkins Hospital inpatient records and/or collection of specimens where there is identifable linkage to the subject require JCCI review. The JCCI RPN must be completed in duplicate and submitted to the CHR for staff processing. C. Full Committee Recommendations on Research Reviewed by CHR After discussing and reviewing the research proposal, the will request the Committee to vote on a course of action. The action must be one of the following: (1) Approved the protocol as submitted. (2) Approve the protocol with the understanding that the research instruments will be reviewed by the Committee prior to initiating direct contact with the subjects. (3) Defer action: 40 (02/92) a. Conditional approval contingent upon the following minor revisions (to be specified). If the revisions are acceptable, the status of the application will be changed to 1 or 2 (above) as appropriate. b. Require significant modification of the protocol before approval. The response will be consideredby the full Committee. C. Invite the investigator to discuss problems with Committee or with designated subcommittee. d. Invite the opinion of an outside consultant who has expertise in the field of research. (4) Reject the protocol (with reasons specified). If the Committee elects to defer action, the principal investigator will be informed of specific problem areas, including the significant modifications required in the protocol. The Committee's decision to "reject a protocol" will result only if the study is incompatible with the Committee on Human Research ethical principles and guidelines on the protection of human subjects. This decision is reached only after a lengthy discussion with the investigator, and only if it is determined that no acceptable compromise can be rendered. d. Communicatiom from the Committee on Human Research The Committee's actions are made part of the record. Formal notice of the Committee action on an application is forwarded by the Committee Chair to the principal investigator within five (5) days of the Committee meeting. Depending on the type of Committee recommendation, the following offices also will be notified of the action: (1) Approve protocol - Statement of Formal Approval; principal investigator, department chair, and the Officefor Research Administration. 41 (2) Approve protocol with research instrument to be submitted in the future - Statement of Formal Approval with notation, principal investigator and department chair. (3) Approval with conditions - The Chair of the Committee notifies the principal investigator, in writing, about the specific minor revisions required for Committee approval. Copies of the correspondence are forwarded to the Committee reviewer(s). (4) Deferred - The Chair of the Committee notifies the principal investigator, in writing, of specific modifications which could enhance the acceptability of the protocol by the Committee on Human Research. Copies of the correspondence are sent to the Committee reviewer(s) and the department chair. (5) Reject - The Chair of the Committee notifies. the principal investigator, in writing, of the specific reasons for which the Committee found the protocol unacceptable. Copies of the correspondence are sent to the Committee reviewer(s), the department chair, and the Office of Research Administration. If the Committee does not receive a response within ninety (90) days to the recommendations conveyed to the principal investigators, the research proposal will be withdrawn from further consideration. If further consideration of the research is requested, the investigator will be required to resubmit it as a new application. Copies of the Statement of Approval are forwarded to the principal investigator and the department chair. The CHR Staff Office notifies the Research Administration Office of the disposition of a research study by signing off on the grant application face sheets (information sheet) after all conditions have been satisfactorily addressed and the study receives final approval. The Research Administration Office will not release any funds until they are notified that the research has been approved by the CHR. 42 (02/92) The Committee on Human Research does not notify funding agencies of the disposition of a protocol. It is the responsibility of the principal investigator to inform the funding agency. (Any application to DHHS must indicate the IRB approval date or exemption number on the PHS 398 or if the application is submitted as pending IRB approval, a follow-up DHHS Form 596 must be submitted by the principal investigator and handledthrough the Research Administration Office.) e. Appeal of Committee on Human Research Decisions The principal investigator may appeal a Committee decision or question a recommendation. This action may be done in writing or by requesting a special hearing at which time additional information and/or supporting testimony of others with expertise in the field may be presented. This hearing may be scheduled for a regular monthly meeting of the Committee, or at the discretion of the chair, at the Executive Subcommittee, or a subcommittee may be appointed to hold a special meeting to review the appeal. The Committee's action based on the subcommittee's recommendation will constitute the final action of the School f. Continuing Review of Applications (1) Changes After Approval It is the obligation of the investigator to inform the Committee as soon as possible about any proposed changes in the approved protocol that may effect human subjects. Proposed changes in a research study are reviewed for initial approval. If the revisions are minor and do not place the study population at risk, the changes will receive expedited approval. (2) Annual Renewal Approval for a research project involving human subjects is valid for one year. All research projects and other related activities involving human subjects are reviewed annually by the Committee. The principal investigator is requested to complete the Annual Renewal Notice, providing the appropriate information on the status of 43 (02/92) the research activity. Procedures for reviewing the response are as follows: a. The response is reviewed by the staff and chair. b. If there are no substantive changes in the protocol, recommendation of approval is made to the full Committee. If there is a significant change in the protocol, however, the study is processed as a new application. c. For studies still collecting data after three years, the Committee conducts a new review, following the procedures for new applications. Included in this review is a consideration of the study's experience to date with human subjects, based on a summary submitted by the principal investigator. d. In the event that the investigator has not returned the Annual Renewal Notice from within by the date it is to be reviewed by the Committee, the investigator, Research Administration and the department chair are notified that if the form is not signed and returned within the next thirty days, approval of the project will be withdrawn.If the investigator subsequently desires to reinitiate work on the project, it must be resubmitted as a new application and it will behandled as any new project. 3. Periodic Review The Committee may request a principal investigator to provide a status report on a more frequent basis than the annual review whenever this is indicated by the nature and degree of apparent risk to human subjects. Periodic reports are reviewed by the full committee to determine whether further action is necessary. IV. General Requirements for Informed Consent; Privacy and Confidentiality, Assessing Risk/Benefit 44 (02/92) A. Informed Consent 1. Federal Regulations a. General Policy Current federal regulations require, as noted in 45 CFR 46, Sec. 46.116, that, with certaia specific exceptions, no investigator may involve a human being as a subject in research covered by these regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject's legally authorized representative. An investigator shall seek consent only undercircumstances that provide the prospective subject or representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence. The information that is given to the subject or the representative should be understandable to the subject or the representative and may not include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject's legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence. b. Disclosure The basic elements of information necessary for consent are stipulated in the regulations as follows: (1) A statement that the study involves research, an explanation of the purposes of the research and the expected duration of the subject's participation, a description of the procedures to be followed, and identification of any procedures which are experimental; (2) A description of any reasonably foreseeable risks or discomforts to the subject; (3) A description of any benefits to the subject or to others which may reasonably be expected from the research; (4) A disclosure of appropriate alternative procedures or courses of treatment, if any, that might be advantageous 45 (02/92) to the subject; (5) A statement describing the extent, if any, to which confidentiality of records identifying the subject will be maintained; (6) For research involving more than minimal risk an explanation as to whether any compensation and an explanation as to whether any medical treatments are available if injury occurs and, if so, what they consist of or where further information may be obtained; (7) An explanation of whom to contact for answers to pertinent questions about the research and research subjects' rights, and whom to contact in the vent of a research-related injury to the subject; and (8) A statement that participation is voluntary, refusal to participate will involve no penalty or loss of benefits to which the subject is otherwise entitled, and the subject may discontinue participation at any time without penalty or loss of benefits to which the subject is otherwise entitled. The regulations further identify six additional elements of information which shall also be provided to each subject, as appropriate. (Specified in 45 CFR 46, Sec. 46.116 (b).) C. Documentation The federal regulations require that, with few exceptions, informed consent must be documented by the use of a written consent form approved by the Institution Review Board (IRB) and signed by the subject or the subject's legally authorized representative. A copy shall be given to the person signing the form The consent form may be either of the following: (1) A written consent document that embodies the elementsof informed consent may be read to the subject or the subject's legally authorized representative, but in any event, the investigator shall give either the subject or the representative adequate opportunity to read it before it 46 (02/92) is signed; or (2) A "short form" written consent document stating that the elements of informed consent have been presented orally to the subject or the subject's legally authorized representative. When this method is used, there shall be a witness to the oral presentation. Also, the IRB shall approve a written summary of what is to be said to the subject or the representative. Only the short form itself is to be signed by the subject or the representative. However, the witness shall sign both the short form and a copy of the summary and the person actually obtaining the consent shall sign a copy of the summary. A copy of the summary shall be given to the subject or the representative, in addition to a copy of the "short form". The federal regulations permit an IRB . to waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either: (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. Each subject will be asked whether the subject wants documentation linking the subject with theresearch, and the subject's wishes will govern; or (2) That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside the research context. In cases where the documentation requirement is waived, the IRB may require the investigator to provide subjects with a written statement describing the research. 2. Policy of the Committee on Human Research a. General Policy The Committee seeks compliance with the federal government's general policy on informed consent, as delineated in the federal regulations. Investigators are expected to comply with these regulations. Specifically, investigators are expected to assure 47 (02/92) that the conditions under which consent is sought to permit subjects to make their own choices about participation - that is, choices which are not manipulated by undue influences or coercive pressures. In addition, investigators are required to give a copy of the consent form to the person signing the form. The Committee in recognitition of the federal regulations permitting waiver of the informed consent requirement in appropriate circumstances The Committee is available to entertain petitions from individual investigators to waive the informed consent obligation or alter aspects of the procedure in a particular case. Investigators should realize that such a request imposes a serious additional responsibility upon the Committee. Investigators should be prepared to provide a detailed justification for a request of waiver. b. Disclosure Investigators are required to disclose to subjects, in language appropriate to subjects' educational level at least the eight items of information stipulated as the basic elements of disclosure in the federal regulations. For research involving more than minimal risk, the Johns Hopkins Medical Institutions have agreed to language to be included in all informed consent statements (see page__) c. Documentation The Committee recognizes that it would inappropriate or impossible as a practical matter for investigators to seek written consent for certain types of research procedures. The Committee reserves the right to decide on a case-by-case basis whether alternatives to written consent are justified. However,the investigator may refer to the following guidelines. (1) Substitution of Oral Consent for Written Consent: In conducting research procedures such as telephone interviews or personal interviews in communities where there is a general distrust of written consent, it may be appropriate to seek oral consent rather than written consent If this alternative is chosen,the following requirements must be fulfilled: 48 (02/92) (a) The study must meet one of two federal conditions for departure from standard documentation procedures (see page__). (b) The interviewer must share with the respondent an oral disclosure covering all the items generally included in obtaining informed consent. This disclosure statement must be approved by the Committee on Human Research. (c) The interviewer must document in writing where that verbal consent has been obtained after the disclosure, has been shared and an opportunity to ask questions has been offered. (2) Implied Consent: (a) Mail Questionnaires: In studies where the only research intervention is a self-administered questionnaire which is mailed to respondents, written informed consent need not be obtained. Instead, the completion and return of the questionnaire is taken as evidence of implied informed consent. Procedures for obtaining implied consent parallel thosein (1), above: a letter or disclosure statement which includes the information necessary to conform to the elements of informed consent must accompany the questionnaire. This statement must be approved by the Committee on Human Research. (b) Questionnaires Self-Administered in the Researcher's presence: Consent issues raised by this research technique may,in certain circumstances, be similar to those raised either by mail questionnaires or personal interviews. (3) Auditor Witnesses-Observers of Consent Process: As the preceding section suggest, the Committee on Human Research and the Federal Government have a strong interest in the content and wording of consent forms (disclosure statements) as well as in consent documentation procedures. The Committee on Human 49 (02/92) Research is, however, concerned with the total consent process including such issues as who solicits consent and under what conditions. The interest here is obviously to assure that the consent obtained is not only informed but also voluntarily or freely given. To protect this interest, the National Commission for the Protection of Human Subjects has recommended that Institutional Review Boards require witnesses or observers to the consent process in certain "high risk" investigations. In accordance with this recommendation, the Committee on Human Research reserves the authority to require such procedures on a selective basis. However, it should be emphasized that the Committee on Human Research has generally not found it necessary to make such requirements. Usually, a detailed description of the consent process including appropriate safegugds against coercion is sufficient. (4) Informed Consent and International Research: If research is to be conducted in cultures where signed statements are mistrusted or are otherwise inappropriateor culturally unacceptable (e.g, illiterate populations),verbal consent or other methods of obtaining consent may be substituted. All procedures specified under guidelines for preparing a disclosure statement (see item 3 below) should be followed. A copy of the disclosure statement in the native language and the cross- translation should be submitted to the CHR. If the investigator feels that any of these procedures are appropriate to the particular setting for any reason (e.g., cultural, ethical or political reasons), the investigator may petition for specific exemption. The Committee realizes that there are often very real problems in obtaining informed consent in other cultures. However, the nvestigator must document the procedures which will be used to assure the voluntary nature of the subjects' participation. The investigator's petition must be detailed and specific and should reflect the special concern of the Committee and of the federal government that investigators should employ the same standards regarding the conduct of research involving human subjects both here and abroad. 50 (02/92) (5) Informed Consent and Minors, the Mentally Disabled, and Prisoners: Consent issues specific to these special populations are handled in the section on Special Population (page 8). 3. General Guidelines for Preparing Disclosure/Informed Consent Statement for Subjects to Participate In Research Projects The broad range of research which involves human subjects makes it impractical to formulate a standard consent form which would be adequate in all circumstances without being cumbersome in many situations. The guidelines which follow have been developed to be used as an aid in drafting and administering the basic consent form and includes provisions which may or may not be required for a given project: The disclosure statement (written in the second person) should address items a. through p. Items q and r pertain to written agreements. a. Specify the title of the study: b. Explain who is conducting the study (the name of the sponsor or institution) and identify the individual (including position and telephone number) carrying out the procedures; c. Explain briefly in comprehensive language, the nature and purpose of the study; d. Explain how the study population was selected (where appropriate); e. Specify the approximate duration of the subject's time in participating the study and the procedures to be used; f. If the study involves a survey, describe the type of information to be gathered and specify if the questions are personal and of a sensitive nature (i.e, personal finances, psychological or emotional experiences,sexual habits, marital and/or family situations, drug or alcohol use, etc.)' g. For studies involving clinical procedures, describe the examinations and tests in which the subject will participate. (e.g., venipuncture - indicate the approximate amount of blood to be drawn, x-rays or radioisotopes - stipulate the dosage and 51 (02/92) explain which it is equivalent to in understandable language,breathing gas; inhalation; exercise, etc.); h. Explain the nature of possible risks, alternate procedures which were considered and why they were not used; i. Explain the possible benefits to be derived from the study to the subject or to society or both, indicate how the benefits outweigh possible harm or risks. (It is important to state the benefits, where appropriate.); j. There may be situations where a patients or research subject is known to possess materials (blood or tissue specimens having unique characteristics thought to have commercial value. If this case, if specimens are to be procured for research purposes, and the investigator expects that the donation will be commercialized into a marketable product, the investigator must inform the subject of the commercial objective before the subject decides whether to donate material to a study. k. Specify that participation in the study is voluntary, that the individual has a right to have all questions answered before and during the study, that the individual has a fight to withdrawn from the study at any time without jeopardizing medical care or employment, etc.; l. If the subject is to be paid for participating in the activity,.indicate the amount and how this was determined; m. Indicate whether confidentiality will be maintained. (Be prepared to explain how confidentiality will be handled.) n. If it is anticipated that the subject may be contacted more than once, this fact should be included in the informed consent statement; o. Specify the approximate time required for each activity included in the study; p. Whenever the project involves a procedures that may result in an injury, it is necessary to specify that neither the Johns Hopkins Hospital, the Johns Hopkins University, nor the Federal Government have a program to provide compensation for persons participating in research projects who may 52 (02/92) experience an injury which is not due to the fault of the investigator (See statement below) q. The informed consent statement (written in the first person) must be signed by the participant and witnesses, unless the investigator provides justification for waiving this requirement; and r. If the study population involves minors or individuals unable to give a valid informed consent, signed permission must be obtained from the parent or legal guardian of the study subject. Where possible, the signature of the minor should also be obtained after the subject has been provided with a full disclosure statement Prospective participants in biomedical and behavioral research should be advised as to the availability or nonavailability of medical treatment or compensation for injuries incurred as the result of such participation The Johns Hopkins Medical Institutions have agreed to the following language to be included in all informed consent statements of projects involving the potential risk of injury: "In the event you believe that participation in the research program has led to an injury, please contact Dr. - (Principal Investigator) at (telephone) or the staff of the Committee on Human Research at 955-3193, either of whom will review the matter with you, identify the medical resources which may be available to you, and assist you in obtaining appropriate medical care. However, The Johns Hopkins University, The Johns Hopkins Hospital and the Federal Government do not have a program to provide compensation for person who may experience an injury while participating in research projects when the injury is not due to the fault of the investigators." B. Privacy and Confidentiality 1. Federal Regulations One of the criteria for Institutional Review Board approval of a research activity in the Federal Regulations (45 CFR 46, Sec 46.111 (7) requires that, where appropriate, "there are adequate provisions to protect the privacy of subjects and to maintain the confidentiality of data" 2. Policy of the Committee on Human Research The Committee on Human Research interprets the above requirement to mean that every effort should be made to minimize the risk that an 53 (02/92) invasion of personal privacy of research subjects will occur. Therefore, investigators should take every precaution to safeguard the personal privacy of potential subjects in searching for participants in their research and to avoid violating assurances of confidentiality which may have been given. Special efforts must be made during the following three phases of research to achieve these goals: a. Access to Records, Data Collection Coding, Data Processing, Editing, Analysis Certain types of research necessitate the review of records. Ideally, the investigator should get the subject's consent prior to accessing the records, however, this is not always possible nor feasible, particularly in epidemiological studies. Investigators have an ethical duty to develop procedures to preserve the confidentiality of information collected. Knowledge of the identity of persons participating in the research project should be limited to only those involved with the project who have a legitimate need to know. The principal investigator has a responsibility to develop a system which restricts access of the identifiers to only such persons. b. Presentation and Publication of the Results of the Research Precautions must be taken when presenting or publishing study results to ensure that individuals are not identifiable through a unique configuration of characteristics even though their names are being omitted. If protection of individual identity is impossible, justification must be provided. C. Maintenance and Retention of Information After the Proposed Research Has Been Completed To the extent that retention of identifiers poses risks to research subjects, the Committee on Human Research recommends that all original forms, cover sheets, cross-reference keys, etc, be destroyed as soon as possible in the course of the study. Naturally, compute related storage files and forms without any identifiers beyond the study number may be kept for further analysis. 54 (02/92) The Committee recognizes that there are certain circumstances in which long-term retention of research records with personal identifiers is necessary. Both the length of time of retention and the nature of the retained information need to be weighed in evaluating a request for retaining records beyond the course of the study. An investigator desiring long-term retention of records with identifiers must request special consideration and provide a statement explaining the uses to be made of the records, the duration of the retention, and justification for such action in terms of risks and benefits. Should long-term retention be approved, the principal investigator is responsible for (i) depositing the identifying cross-reference key with the Dean's Office for storage, and (ii) filing the research records without identifiers with the investigator's academic department. 3. Suggested Procedures for Maintaining Confidentiality a. One method for protecting the identity of study subjects thathas worked well for many investigators in the following: (1) Design the format of the questionnaire and/or record abstract forms so that identifying information,such as name, exact street address, telephone number, hospital history number, etc, is recorded on a detachable "cover" sheet. (2) Assign each subject a unique study number which will appear on each page of the recording form (3) After the form has been completed, detach the cover sheet and compile a cross-reference key between study numbers and individual identities. The remainder of the form can then be handled by numerous coders, keypunchers, clerical staff, and others without the identity of the subject being made known to them. However, should the identity of the subject be needed in order to verify questionable or incomplete data a tracing mechanism will exist. (4) Keep the key and cover sheets in a safe, locked area with access restricted to the principal researcher and those who have a legitimate need to share access. b. Safegaurding Confidentiality of Records 55 (02/92) The Committee on Human Research requires that investigators advise potential subjects about procedures for safeguarding confidentiality of the data obtained. Particular attention should be paid to the language in the disclosure statement or consent form so that the subject is not misled inadvertently into believing confidentiality is assured when in fact it is beyond the power of the investigator to provide such assurance. A research has limited ability to guarantee confidentiality, especially in studies eliciting information about illegal sensitive, or socially unacceptable activities, where there is a possibility of legal consequences. There may be cases where access to the data can be obtained over the objections of the researcher. Therefore, it is important to initiate innovative measures to maintain anonymity of participants. The most common means of legally compelling disclosure of information is by use of the subpoena power of a court legislative body or government agency. In general federal and state regulations do not protect research material from subpoena. However, certain types of research may qualifies for protection from disclosure under one of three types of exemption certifications: (1) Confidentiality Certificate from the Alcohol Drug Abuse and Mental Health Administration DHHS (2) Grant of Confidentiality from the Drug Enforcement Administration, Department of Justice (3) Privacy Certification from the Law Enforcement Assistant administration Researchers are urged to apply for the above protection against disclosure from the appropriate federal agency. If a subpoena is addressed to a researcher or served on a research as an agent of the University, he or she should contact the University's General Counsel immediately for guidance and legal representation. Under no circumstances should an investigator disclose information in response to a subpoena without consulting with the General Counsel. 56 (02/92) c. In discussing confidentiality in the consent statement, the following language is suggested for consideration: (1) "... every effort will be made to safeguard the confidentiality of the information provided," (2) "... every possible measure will be taken to safeguard the confidentiality of the information provided insofar as it is legally possible." d. General Guidelines for Safeguarding Confidentiality (1) Studies Involving Surveys: (a) All identifying information should be removed from the survey instrument prior to the coding of the data. (b) If there will be a code to like identifying information to the respondent, describe the system by which this code will be maintained (i.e, where it will be kept, who will have access to it, etc.). (c) If no such code will be used indicate what will happen to the original identifying information and who will have access to it. If it is to be retained, state for what purpose. (d) If the study involves a follow-up, how will the follow-up be handled? Indicate whether by additional interview, record study, etc. (e) Describe the system that will be used to maintain the follow-up data. (f) If the material is to be published, what form will it take? How will anonymity be assured? (g) Indicate how the data and identifying information will be destroyed at the termination of the study. (2) Studies Involving the Use of Records: 57 (02/92) (a) Indicate what the source of the data for the study will be and how this data will be obtained. (b) Describe the system by which this data will be maintained. (c) Will it be necessary to record any identifying information from the records? (i) If yes, sprcify the type of information that will be required and for what purpose. (ii) Explain how this information will be maintained. (d) If the study requires follow-up, describe the procedures that will be used. to conduct it. Indicate the individual(s) who would be responsible for carrying out those procedures. (e) Indicate who will have access to the records and/or identifying information during the study. (f) If the data is to be published, what form will it take? How will anonymity be assured? (g) Indicate how the data and identifying information will be destroyed at the termination of the study. C. Risk-Benefit Considerations 1. Federal Regulations The Institutional Review Board is responsible for determining whether the risks to the subject are outweighed by the sum of the anticipated benefit to the subject and the importance of the knowledge that amy reasonable be expected to be gained as to warrant a decision to allow the subject to accept these risks. 2. Policy of the Committee on Human Research In order to implement the federal regulations in this area, the Committee on Human Research policy requires that the nature of the (or the Potential for harm) be clearly identified; that any 58 (02/92) potential benefits accruing to the subject as a result of participation in the research be clearly established; and that the nature and the importance of the knowledge to be gained as a result of the research be enunciated. In minimal risk studies, the Committee has acted to interpret either benefits to the individual or the importance of the research as factors which might outweigh those minimal risks to human subjects. When there is, however, any substantial risk involved in a study, the potential benefits of the subject are weighed most heavily. The importance of the research as well as the scientific merit of the research proposal must frequently be considered to determine whether the research outcome can truy be expected to provide a "benefit to society" which could be summed with the benefit to the individual to outweigh the potential for harm to the subject 59 (02/92) APPENDIX A DECLARATION OF HELSINKI I. BASIC PRINCIPLES The principles stated in the Helsinki, adopted by The School of Hygiene and Public Health, have been modified by replacing the word "doctor" with the word "researcher".) 1. Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on adequately performed laboratory and experimentation and on a thorough knowledge of the scientific literature. 2. The design and performance of each experimental procedure involving human subjects should be clearly formulated in an experimental protocol which should be transmitted to a specially appointed independent committee for consideration, comment and guidance. 3. Biomedical research involving human subjects should be conducted only by scientifically qualified persons and under the supervision of a clinically competent medical person. The responsibility for the human subject must always rest with a medically qualified person and never rest on the subject of the research, even though the subject has given his or her consent. 4. Biomedical research involving human subjects cannot legitimately be carried out unless the importance of the objective is in proportion to the inherent risk to the subject. 5. Every biomedical research project involving human subjects should be preceded by careful assessment of predictable risks in comparison with foreseeable benefits to the subject or to others. Concern for the interests of the subject must always prevail over the interest of science and society. 6. The right of the research subject to safeguard his or her integerty must always be respected. Every precaution should be taken to respect the privacy of the subject and to the impact of the study on the subject's physical and mental integrity and on the personality of the subject. 7. Researchers should abstain from engaging in research projects involving human subjects unless they are satisfied that the hazards involved are believed to be predictable. Researchers should cease any investigation if the hazards are found to outweigh the potential benefits. 60 8. In publication of the results of his or her research, the researcher is obliged to preserve the accuracy of the results. Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication. 9. In any research on human beings, each potential subject must be adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and discomfort it may entail. He or she should be informed that he or she is at liberty to abstain from participation in the study and that he or she is free to withdraw his or her consent to participation at any time. The researcher should then obtain the subject's freely given informed consent,preferably in writing. 61 (02/92) THE JOHNS HOPKINS UNIVERSITY OFFICE FOR RESEARCH SUBJECTS COMMITTEE ON HUMAN RESEARCH (New Project or Third Year Renewal) CHR No.____________ Check One: New Research Project______ Amendment______ Program/Training Grant______ Course Activity______ Principal Investigator:__________________________________ Dept./Room__________ (Must be a Faculty Member) Co-Investigator(s):______________________________________________ _____________ Student Investigator:____________________________________________________ _____ Project Title:___________________________________________________________ _____ _________________________________________________________________ _____________ _________________________________________________________________ _____________ SECTION ONE: Studies which require Joint Committee on Clinical Investigation (JCCI) Review. (School of Medicine). If you answer YES to any of the following questions, the JCCi Research Project Notification (RPN) should be completed (forms can be obtained in Room 1606 Hygiene). Forward the original and two copies of the RPN application to the Office for Research Subjects for processing. Otherwise, continue with the CHR application form. Yes No ___ ___ 1. Does the study involve Johns Hopkins Hospital or Francis Scott Key patients (in or outpatients) as subjects/participants? ___ ___ 2. Does the study involve Johns Hopkins Hospital or Francis Scott Key medical records or staff? 3. Does the study involve the use of ___ ___ a. human exposure to radioactive agents? ___ ___ b. human exposure to infectious agents? ___ ___ c. fetal tissue or abortus? ___ ___ d. investigational new drugs (IND)? ___ ___ e. investigational new device (IDE)? SECTION TWO: Exempt Research Studies - If you are submitting this protocol for consideration under the exempt research category, please check here____, answer questions one through five and complete the full application. Once the Committee makes a determination of exempt status, a statement of exempt certification will be issued. Yes No 1. Does the research involve ___ ___ a. the use of existing data, or pathological or diagnostic specimens only? ___ ___ b. and interview or questionnaire only? ___ ___ c. observation of public behavior only? ___ ___ 2. Are the specimens or data publicly available via public archives or obtained via public source? ___ ___ 3. Is the information recorded by the investigator in such a manner that subjects cannot be identified from information provided directly or through identifiers linked to the subjects? ___ ___ 4. Does the research deal with sensitive aspects of the subject's own behavior; sexual behavior, alcohol user or illegal conduct such as drug use. 5. If the information recorded about the individual became known outside of the research ___ ___ a. could the subject be paced at risk or criminal or civil liability? ___ ___ b. could the subject's financial standing,reputation or employability be damage? SECTION THREE: Funding Yes No ___ ___ Is any support for the project anticipated? Sponsor Name:_____________________________________________ Do any of the participating investigators and/or their immediate families have an equity relationship (e.g. stockholder) with the sponsor of the project or manufacturer and/or owner of the test product or device to be studied or serve as a consultant to ___ ___ any of the above? If YES, submit a written statement of disclosure to the Sponsored Projects. Office. ________________________________________________ ____________ Signature of Principal Investigator Date ________________________________________________ ____________ Signature of Department Chair Date (over) RESEARCH PLAN The following items should be covered in NO MORE THAN THREE TYPED PAGES and presented in consecutive order. Include on copy of the human subject's section of the grant and/or the proposal that this application references. If there is not, please so state here _____________________________. 1. SPECIFIC RESEARCH QUESTIONS TO BE ADDRESSED BY THIS PROTOCOL: _________________________________________________________________ ______________ _________________________________________________________________ ______________ _________________________________________________________________ ______________ 2. RATIONALE: State the problem, the background and the aim o the proposal as it relates to the research question. 3. PROTOCOL: Describe the study design, including the population (sex, age and locale of the participants). Identify all procedures as they relate to the step by step activity of the subjects involved. Distinguish procedures which are part of routine care from those which are part of the experimental design. Include the methods used to assess the results and impact of the study. If the procedures include the use of a questionnaire or interview instrument, a copy of the instrument is to be appended to this application. If the instrument is in the developmental phase, then provide and outline of the types of questions to be asked and the expected date of completion and submission to the Committee. 4. RISKS/BENEFITS: Describe all major and minor risks (physical, psychological, social) and their anticipated frequency. Detail any measures that will be taken to minimize risks and deal with any unanticipated results. Address the level of research burden (including inconvenience to subjects). Describe how subjects may benefit from participation in this study, as well as the significance and likelihood of benefit to others or to scientific knowledge. If there are no benefits to subjects from participation in this study, state so. 5. CONSENT PROCEDURES: Describe the process by which the consent of potential subjects will be solicited, including how subjects will be solicited, including how subjects will be approached and by whom. Written consent must be obtained from all participating research subjects (or their parents/guardians). (If children, a copy of the assent form is to be included - varies with age). Any request to waive the obligation to consent in writing (or to waive consent altogether) must be accompanied by a justification for this waiver. If consent to be solicited in a foreign language, a copy of the consent form in that language and a back translation in English is to be provided. The guidelines for consent and assent forms are attached; forms must be submitted with this application for Committee review and approval. The consent form is to be typed on the form provided. No substitutions will be accepted. If applicable, a copy of IRB approval from other institutions should be attached. 6. DISCLOSURE LETTERS and CONSENT SOLICITATION BY TELEPHONE: If an advance letter and/or consent solicitation by telephone is to be used in lieu of or in addition to the consent process, provide justification for the use of this procedure; specify at what point in the study this document/procedure will be introduced to potential subjects and by whom. Advance letters and "scripts" or the disclosure to be made by telephone must be submitted with the application for Committee review and approval. 7. CONFIDENTIALITY: Describe the methods for safeguarding the confidentiality of the study data and/or the measures for protecting the anonymity of the subjects. Include a description of the plans for record keeping and data security; who will have access to identifying information; and plans for disposal at the completion of the study. Location of the stored data:_______________________________________ Person Responsible and Telephone Number:___________________________ 8. COLLABORATION: Provide letters certifying approval of collaborators and their respective sites of operation,, other institutional IRBS, (if applicable) AND/OR health ministries (if applicable) for international research.(An IRB approval from another institution on a collaborative study does not preclude JHU review and approval). THREE COPIES OF THE APPLICATION and ONE COPY OF THE HUMAN SUBJECT'S SECTION OF THE GRANT/PROPOSAL/THESIS SHOULD BE COMPLETED AND SENT TO: THE OFFICE FOR RESEARCH SUBJECTS COMMITTEE ON HUMAN RESEARCH The Johns Hopkins University - School of Hygiene and Public Health Room 1606, 615 North Wolfe Street Baltimore, Maryland 21205 COMMITTEE ON HUMAN RESEARCH GENERAL GUIDELINES FOR PREPARING THE "EXPLANATION OF RESEARCH PROJECT TO SUBJECT" SECTION OF A CONSENT FORM FOR CLIENT INVESTIGATION Consent form explanations for research projects must be typed on the standard JHU/CHR Consent Form. If continuation pages are necessary, the explanation may be continued on a plain sheetof paper. Additional pages should be clearly numbered and should contain both the title of the project and the name of the principal investigator typed at the top of the page(s). The explanation should be written as if the investigator were speaking to the subject; avoid speaking for the subject with statements like "I understand that. . ." The Committee believes use of first person in the explanation is manipulative and puts words in the mouths of subjects. Subjects may not understand the explanation, but when it is written in the first person they may be too embarrassed to ask questions.It is preferable to have the explanation written in second or third person in language appropriate to the reading level of the study population and in the native language, if in a foreign country. In the interest of simplicity, use separate consent forms for subject subgroups. A separate consent form is attached. The sample illustrates how to organize the explanation of the project to include all of the required elements of a consent form. Please use paragraph headings to organize the explanation. If you have any questions about the recommendations for preparation of consent forms, please contact the Committee on Human Research Staff Office at 955-3193. (4/91) SAMPLE CONSENT FORM The Johns Hopkins University School of Hygiene and Public Health Committee on Human Research REQUIRED ELEMENTS OF INFORMED CONSENT FORM. MOST CONSENT DOCUMENTS MAY BE COMPRISED OF SIX OR SEVEN PARAGRAPHS WHICH ADDRESS THE FOLLOWING POINTS: TITLE OF RESEARCH PROJECT: EXPLANATION OF RESEARCH PROJECT PURPOSE OF STUDY: Explain the purpose of the research project. Explain why/how the volunteer/patient was selected for the study and inform him/her why he/she is being asked to participate in this study. PROCEDURES: State the procedures to be used if the subject agrees to participate in the study. Specify the approximate total duration of the subject's time to participate; approximate time required for each activity; and any plans to contact more than once or for possible follow-up studies. If the study involves a survey, describe the type of information to be collected; specify if the questions are personal or of a sensitive nature (e.g. personal finances, psychological or emotional experiences, sexual habits, marital and/or family situations, alcohol or illegal drug use, etc). For studies involving clinical procedures, briefly explain the study design; describe the examinations and tests in which the subject will participate (e.g. venipuncture - specify the number, amount of blood to be drawn in household measures such as tsp; cup; etc.) Explain how treatment groups will be assigned. If treatment assignments are determined by randomization, the process should be defined for subjects, i.e. either by drawing a card or number, or by flipping a coin. State what procedures will be done solely for research purposes and/or what is innovative in the project. RISK/DISCOMFORTS: Describe all major and minor risks (physical, psychological, social) and their anticipated frequency as well as any research-related inconveniences. Detail any measures that will be taken to minimize and deal with risks or any unanticipated results. BENEFITS: State potential benefits of participation for the subject. Do Not Overstate Benefits - Be Realistic. If a subject will not benefit from participation, clearly state so. State possible general benefit for science or for other subjects with similar diseases or for the population, at large, (if applicable). Outline remuneration amount and payment procedure, including penalties for failure to complete the study (if applicable). There may be situations where a patient or research subject is known to possess materials (blood or tissue specimens) having unique characteristics thought to have commercial value. If these specimens are obtained for research purposes and are expected to be commercialized into a marketable product, subjects must be informed of the commercial objective prior to deciding whether to donate the sample for a study. ALTERNATIVES TO PARTICIPATION: (May be omitted for normal volunteer studies) Explain realistic alternatives to participation; specifically, state what treatment will be offered or recommended if patient declines to participate. THIS CONSENT FORM CONTINUES ON THE REVERSE SIDE (4/91) CONFIDENTIALITY Describe the procedures for protecting the confidentiality of the information collected from the subject. Specify who will have access to the data; how and when personal identifiers will be destroyed. It is suggested that you include the following language in all consent forms except where subjects are strictly anonymous. "Every effort will be made to protect the confidentiality of the information provided insofar as it is legally possible." If there is reason to suspect that the data may be of interest in a legal proceeding, the reference to "limits of the law" should be amplified. If a Certificate of Confidentiality has been issued to protect the data from subpoena, include this information in the consent form. NOTE: A compensation clause for injury is printed on Page Two of the Consent Form. Whenever a project involves a procedure that may result in an injury to the participant, prospective subjects should be advised as to the availability or nonavailability of medical treatment or compensation. A specific statement to address the issue of compensation for protocols involving the potential risk of injury is included in paragraph two, below the dotted line. The following information is printed on all consent forms approved and stamped by the Committee on Human Research. The blank lines should be filled-in as appropriate for each individual project (if not applicable, write n/a in the blank). If continuation pages are necessary, additional pages should be clearly numbered and should contain both the title of the project and the name of the principal investigator typed at the top of the page(s). SAMPLE Your participation in this research project is completely voluntary. You have the right to withdraw from the research study at any time. Even if you do not want to join the study, or if you withdraw from the study, you will still receive the same quality of medical care available to you at . Your decision also will not jeopardize your employment at . You should ask the principal investigator listed below any questions you may have about this research study. You may ask him/her questions in the future if you do not understand something that is being done. The investigators (or doctors) will share with you any new findings that may develop while you are participating in this study. If you want to talk to anyone about this research study because you think you have not been treated fairly or think you have been hurt by joining the study, or you have any other questions about the study, you should call the principal investigator, at or call the Office for Research Subjects at (301) 955-3193. Either the principal investigator or the people in the IRB office will answer your questions "and/or help you find medical care if you feel you have suffered an injury. The Johns Hopkins University, The Johns Hopkins Hospital and the Federal Government do not have any program to provide compensation to you if you experience injury or other bad effects which are not the fault of the investigators." If you agree to participate in this study please sign your name below. Subject's signature (including children, when applicable) Signature of Parent or Guardian (when applicable) Witness to Consent Procedures* Signature of Investigator Date *Optional unless subject is illiterate, or unable to sign Note: Signed copies of this consent form must be a) retained on file by the Principal Investigator, b) given to the participant and c) put in the patient's medical record (when applicable). (4/91) NOT VALID WITHOUT THE COMMITTEE OR IRB STAMP OF CERTIFICATION Void One Year From Above Date CHR No. COMMITTEE ON HUMAN RESEARCH CONSENT FORM The Johns Hopkins University School of Hygiene and Public Health Title of Research Project: CHR# Explanation of Research Project: THIS CONSENT FORM CONTINUES ON THE REVERSE SIDE (4/91) Side Two Your participation in this research project is completely voluntary. You have the right to withdraw from the research study at any time. Even if you do not want to join the study, or if you withdraw from the study, you will still receive the same quality of medical care available to you at . Your decision also will not jeopardize your employment at . You should ask the principal investigator listed below any questions you may have about this research study. You may ask him/her questions in the future if you do not understand something that is being done. The investigators (or doctors) will share with you any new findings that may develop while you are participating in this study. If you want to talk to anyone about this research study because you think you have not been treated fairly or think you have been hurt by joining the study, or you have any other questions about the study, you should call the principal investigator, at or call the Office for Research Subjects at (410) 955-3193/FAX (410) 955-0258. Either the principal investigator or the people in the IRB office will answer your questions and/or help you find medical care if you feel you have suffered an injury. The Johns Hopkins University, The Johns Hopkins Hospital, and the Federal Government do not have any program to provide compensation to you if you experience injury or other bad effects which are not the fault of the investigators. If you agree to participate in this study please sign your name below. Subject's signature (including children, when applicable) Signature of Parent or Guardian (when applicable) Witness to Consent Procedures* Signature of Investigator Date *Optional unless subject is illiterate, or unable to sign Note: Signed copies of this consent form must be a) retained on file by the Principal Investigator, b) given to the participant and c) put in the patient's medical record (when applicable). (4/91) NOT VALID WITHOUT THE COMMITTEE OR IRB STAMP OF CERTIFICATION Void One Year From Above Date CHR No. PARENTAL CONSENT/CHILD ASSENT GUIDELINES It is the Committee on Human Research policy that, in addition to parental consent, the assent of children ages 5 or older must be obtained. CONDITIONS: "Children" - are persons who have not attained the legal age for consent to treatments or procedures involved in the research, under the applicable laws of the jurisdiction in which research will be conducted. The age of majority in the State of Maryland is 18 years. The exception to the 18 year-old cutoff is an "emancipated minor." "Emancipated Minors" - include those persons who are not living with a parent and who are financially independent from the parent. Pregnant adolescents who seek prenatal care, and those who seek medical care (without the parent's knowledge) for a sexually transmitted disease are also considered exceptions when the research relates to that clinical care. "Assent" - means the child's affirmative agreement to participate in research. Mere failure to object, absent affirmative agreement, should not be construed as assent. "Parent" - means the child's biological or adoptive parent. "Guardian" - means an individual who is authorized under applicable State or local law to consent on behalf of a child to general medical care. It is Committee on Human Research policy that, with the exception of "emancipated minors" and research relating to clinical services available to children without parental consent (see above), parental consent (or guardian consent) must be obtained for all studies involving children. In addition, the assent of children aged five and older also must be obtained. The Committee recognizes that the formulation of assent procedures and forms for children is difficult. We suggest different approaches for each of four age ranges. 1) Children younger than 5 years: A simple oral explanation of the study should be offered to the child before study-related procedures are conducted. (For a blood drawing study, for example: "We have to draw some blood for . That means you will feel a little needle stick. It will only hurt for a minute. Your mom (or dad) will be with you the whole time.") 2) Children between the ages of 5 and 12 years: Informed voluntary assent should be obtained without pressure from parents or investigators. The CHR application should include an example of the explanation to be offered to the child. Assent from the child should be solicited in the presence of a parent, and the parental consent form should include the following statement from the investigator: "This project has been explained to my child in my presence, in language, he/she can understand. He/she has been encouraged to ask questions both now and in the future, about the research study." 3) Children between the ages of 12 and 16 years: Investigators may choose to handle the consent/assent requirements for this group in one of two ways. They may either submit a consent form that is written at a level simple enough for both parent and child to read meaningfully (i.e. about a 5th grade reading level) or they may choose to submit a consent form for the parents and a separate assent form for the child to read and sign. If a consent form is designed for both the parent and child, the form should be signed by each after the study has been explained. An assent form should be written as simply as possible and cover the following points: a) what the study is about b) why he/she qualifies for the study c) what procedures will be done d) potential benefit e) potential risks f) an assurance that he/she will be treated the same whether or not he/she agrees to join the study g) an invitation to ask questions h) assurance that he/she may withdraw from the study after discussing it with his/her parents. 4) Children between the ages of 16 and 18 years: A consent form written in language that is easily understandable for both the parents and the child is sufficient for this group. A separate assent form need not be used. The parent and child must sign the consent form. (4/91)