Preparing the human subjects research section of the research plan for Grant Applications (PHS 398)

1. Preparing the human subjects research section of the research plan for Grant Applications (PHS 398) Created by the Humans and Animal Research Protections Office (HARPO) Email: HARPO@umbc.edu

2. Purpose of the tutorial To assist investigators with the preparation of the supplemental instructions for preparing the human subjects section of the research plan for the PHS 398. Complete instructions are available at: http://grants1.nih.gov/grants/funding/phs398/instructions2/phs398instructions.htm

3. Instructions Part II of the PHS 398 is to be used if a proposed research project will involve human subjects. The NIH instructions will help in determining whether human subjects are involved and include six possible scenarios and detailed instructions to assist you in completing the Research Plan. These supplemental instructions were added to the PHS 398 grant application packet in September, 2004.

4. Preparing the Research Plan In the Human Subjects Research section of the Research Plan, investigators must provide sufficient information for reviewers to determine that the proposed research meets: (1) the requirements of the HHS regulations to protect human subjects from research risks (45 CFR Part 46), (2) the requirements of NIH policies for data and safety monitoring of clinical trials, and (3) the requirements of NIH policies on inclusion of women, minorities, and children. If the research is exempt from the requirements in the Federal regulations, investigators must provide sufficient justification for the exemption. This will allow a determination by peer reviewers and NIH staff that claimed exemption(s) is/are appropriate.

5. Preparing the Research Plan Applications must comply with this requirement; if not, application processing may be delayed or the application may be returned to the applicant without review

6. Preparing the Research Plan For all research involving human subjects, a part of the peer review process will include careful consideration of protections from research risks, as well as the appropriate inclusion of women, minorities, and children. The Scientific Review Group (SRG) will assess the adequacy of safeguards of the rights and welfare of research participants, and the appropriate inclusion of women, minorities, and children, based on the information in the application.

7. Questions to ask and scenarios to use To assist investigators in filling out this section of the application, a Decision Table is provided that presents six possible scenarios. All research projects will fall into one of these six scenarios. Determining which scenario best matches the proposed research depends on an investigator’s answers to the following five questions. For more information about each scenario, click on the highlighted link, review, then hit the Back button of your browser to return to this tutorial (click “Open”).

8. Question 1: Does the proposed research involve human subjects? The HHS regulations "Protection of Human Subjects" (45 CFR Part 46, administered by OHRP) define a human subject as a living individual about whom an investigator conducting research obtains data through intervention or interaction with the individual or Identifiable private information http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question1_human_subjects.htm

9. Question 2: Does the proposed human subjects research meet the criteria for one or more of the exemptions in the HHS Regulations (45 CFR Part 46)? PART 1 Human subjects research is exempt if all of the proposed research meets the criteria for one or more of the following six exemptions (brief descriptions below): Exemption 1: Research conducted in established or commonly accepted educational settings, involving normal educational practices…. Exemption 2: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior…. Exemption 3: Research involving the use of educational tests (cognitive, diagnostic, aptitude, achievement), survey procedures, interview procedures, or observation of public behavior, if the human subjects are elected or appointed public officials or candidates for public office….. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question2_exempt_research.htm

10. Question 2: Does the proposed human subjects research meet the criteria for one or more of the exemptions in the HHS Regulations (45 CFR Part 46)? PART 2 Human subjects research is exempt if all of the proposed research meets the criteria for one or more of the following six exemptions (brief descriptions below): Exemption 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…. Exemption 5: Research and demonstration projects that are conducted by or subject to the approval of Department or Agency heads and that are designed to study, evaluate, or otherwise examine: (i) public benefit or service programs…. Exemption 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….. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question2_exempt_research.htm

11. Question 3: Does the proposed research meet the definition of Clinical Research? The NIH defines Clinical Research as: • Patient-oriented research. Research conducted with human subjects (or on material of human origin such as tissues, specimens and cognitive phenomena) for which an investigator (or colleague) directly interacts with human subjects. Excluded from this definition are in vitro studies that utilize human tissues that cannot be linked to a living individual. Patient-oriented research includes: (a) mechanisms of human disease, (b) therapeutic interventions, (c) clinical trials, or (d) development of new technologies. • Epidemiologic and behavioral studies. • Outcomes research and health services research. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question3_clinical_research.htm

12. Question 4: Does the proposed research include a Clinical Trial?PART 1 The NIH defines a clinical trial as a prospective biomedical or behavioral research study of human subjects that is designed to answer specific questions about biomedical or behavioral interventions (drugs, treatments, devices, or new ways of using known drugs, treatments, or devices). Clinical trials are used to determine whether new biomedical or behavioral interventions are safe, efficacious, and effective. Behavioral human subjects research involving an intervention to modify behavior (diet, physical activity, cognitive therapy, etc.) fits these criteria of a clinical trial. Will require a Data and Safety Monitoring Plan http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question4_clinical_trial.htm

13. Question 4: Does the proposed research include a Clinical Trial?PART 2 Biomedical clinical trials of experimental drug, treatment, device or behavioral intervention may proceed through four phases: Phase I clinical trials test a new biomedical intervention in a small group of people (e.g., 20-80) for the first time to evaluate safety (e.g., to determine a safe dosage range, and to identify side effects). Phase II clinical trials study the biomedical or behavioral intervention in a larger group of people (several hundred) to determine efficacy and to further evaluate its safety. Phase III studies investigate the efficacy of the biomedical or behavioral intervention in large groups of human subjects (from several hundred to several thousand) by comparing the intervention to other standard or experimental interventions as well as to monitor adverse effects, and to collect information that will allow the intervention to be used safely. Phase IV studies are conducted after the intervention has been marketed. These studies are designed to monitor effectiveness of the approved intervention in the general population and to collect information about any adverse effects associated with widespread use. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question4_clinical_trial.htm

14. Question 5: Does the proposed research meet criteria for an NIH-Defined Phase III Clinical Trial? An NIH-Defined Phase III Clinical Trial is a broadly based prospective Phase III clinical investigation, usually involving several hundred or more human subjects, for the purpose of either evaluating an experimental intervention in comparison with a standard or control intervention or of comparing two or more existing treatments. The definition includes pharmacologic, non-pharmacologic, and behavioral interventions given for disease prevention, prophylaxis, diagnosis, or therapy. Community trials and other population-based intervention trials are also included. If your research meets the above criteria, then in addition to providing a Data and Safety Monitoring Plan, you will be expected to address whether you expect to find clinically important sex/gender and/or race/ethnicity differences in the intervention effect. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_question5_nih_phase3_clinical_trial.htm

15. Further information on Exemption # 4 Research that meets the criteria for Exemption 4 is Human Subjects Research, but it is not considered clinical research. Exemption 4 includes research projects 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. http://grants1.nih.gov/grants/funding/phs398/instructions2/p2_exemption4_guidance.htm

16. Further information on Exemption # 4 • “Existing" data or specimens must be "on the shelf" (or in the freezer) at the time the protocol is submitted to the IRB. Exemption 4 applies to retrospective studies of specimens and/or data that have already been collected. • “Publicly available sources” means public sources of data, such as census data. While debatable, organizations that make human cells and tissues broadly accessible to the research community are not generally considered to be publicly available. • “Identifiers linked to the subjects” are names, social security numbers, medical record numbers, or pathology accession numbers, or other codes that permit specimens to be linked to living individuals and perhaps also to associated medical information.

17. How to determine if research meets the criteria for Exemption 4 The humans subjects regulations decision charts (http://www.hhs.gov/ohrp/humansubjects/guidance/decisioncharts.htm) from the Office of Human Research Protection (OHRP) will help to determine research falls under the human subjects regulations and if so, whether a research project meets the criteria for Exemption 4 But, OHRP advises that investigators do not have the authority to make an independent determination that research involving human subjects is exempt. IRBs are designated to make this determination. Investigators need to review the OHRP guidance and work with the IRB to make that final determination

18. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario A

19. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario B

20. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario C

21. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario D

22. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario E

23. Decision Table for Human Subjects Research, Protection and the Inclusion of Women, Minorities, and ChildrenScenario F

24. Other human research guidance from the NIH NIH implementation of Office for Human Research Protections (OHRP) guidance on research involving coded private information or biological specimens • NOTICE: NOT-OD-05-020http://grants.nih.gov/grants/guide/notice-files/NOT-OD-05-020.html

25. Questions? Contact the Human and Animal Research Protections Office (HARPO) at 410-455-2737 or email at: HARPO@umbc.edu