• Background and rationale
• Objectives or purpose
• Study methodology (including description of the study groups or arms, if applicable)
• Subject characteristics
• Endpoints to be measured
• Description of intervention, follow-up, and duration of study
• Comment about statistics and plans for analysis

• We are conducting a clinical trial to measure the safety and effectiveness of Drug X in people who are at high risk for heart disease. Heart disease is the leading cause of death in the United States, and controlling certain risk factors may prevent or delay the development of heart disease. We will compare two groups of subjects: (1) a control group will be instructed to follow the American Heart Association Step One diet and will take a pill that contains no active ingredients (a placebo), and (2) a treatment group will be instructed to follow the American Heart Association Step One diet and will take Drug X. The subjects will be assigned to a group randomly, like flipping a coin, and neither they nor the investigators will know which group they are in. The subjects will come to the clinic for study visits three times a year for 5 years. Statistical comparisons will be made between the two groups in terms of blood lipids, blood pressure, and cardiac events (heart attack, heart failure, and stroke).
• The objectives of this study are twofold. First, we will investigate the ways in which homeless adolescents make meaning and create their identity based on their daily experiences. Second, this data will be used to help inform and extend research, policy, and practice related to assisting homeless adolescents’ transition to adulthood. This project gives voice to the experiences of homeless youth and documents their lives as they move towards adulthood. The goal of this study is to develop research driven policies regarding homeless youth.

12.1. Describe in detail the design and methodology of the study. If applicable, include information on stratification or randomization plans. Identify and distinguish between those procedures that are standard of care and those that are experimental. Include the frequency and duration of each activity and the total length of subject participation. (HSC: refer to specific sections of the protocol/grant, if applicable)

Clearly describe the research design and all of the procedures that will be used to accomplish the specific aims of the research. Include the following types of information:

An Example of Study Design / Methodology for Social-Behavioral Research:

• In this qualitative study, I will use an ethnographic approach to study the socialization and culture of graduate students. I will utilize four methods to collect data: document analysis, observation, interviews, and focus groups. The majority of data collection will occur in the Fall semester.
  
  
• Interviews will take place from September through December. Students will be interviewed twice during the fall semester: once during September or early October and a second time in November or December. 20 to 25 students per department (for a total of 40-50 students) will be interviewed. Of these 50 students, 40 will be men and 10 will be women. (5 women will be interviewed in each department.) The Interviews will last between 45 and 90 minutes.
  
  
• Five to seven faculty and staff members per department will be interviewed once during the Fall semester. The interviews will last between 30 and 45 minutes.
  
  
• Focus groups will occur at the beginning of the Spring semester. I will conduct one focus group per department (for a total of 2 focus groups). Participation will be capped at eight students per focus group. Focus groups will last from 60 to 90 minutes.

INSTRUCTIONS FOR BIOMEDICAL RESEARCH:

  You must include:

• The type of research design that will be used (for example, placebo controlled, randomized, double-blind, Phase I/II//III, single subject case report, or crossover design).
  
• All procedures that will be conducted with human subjects. Describe the procedures in chronological order and provide the frequency and duration of each procedure.
  
• Amounts of specimens to be collected, if applicable (for example, 5 ml of blood at each of the four study visits).
  
• For clinical studies, clearly indicate the procedures that are considered to be part of routine care and those that are considered experimental (performed for the purposes of the study only).
  
• If applicable, identify the sources of the research materials (specimens, records, or data). Explain if the materials will be obtained specifically for research purposes or collected for other purposes (for example, medical records of routine care).
  

12.1.a. If needed, copy-and-paste any tables here and reference in the question above.

HSC only: If there are existing tables in the research proposal, protocol, or other study document that describe the statistical analysis, please refer to the page number or section of the document where the tables can be found, rather than copying and pasting them into the application.

If there are additional supporting documents that are necessary for the review of this application, please upload them to section 40.1 (e.g. tables, diagrams, pictures, spreadsheets, etc.).

12.2. Provide a detailed description of the planned data collection, specific outcomes, and criteria for evaluation and endpoint definition. (HSC: refer to specific sections of the protocol/grant, if applicable)

Describe the type of data you will collect and how you will collect and record the data. Describe the specific outcomes you will evaluate in your study.

For clinical intervention studies, describe the primary and secondary outcomes that will be used to assess the effectiveness of the research treatment.

12.2.a. If needed, copy-and-paste any tables here and reference in the question above.

HSC only: If there are existing tables in the research proposal, protocol, or other study document that describe the statistical analysis, please refer to the page number or section of the document where the tables can be found, rather than copying and pasting them into the application.

If there are additional supporting documents that are necessary for the review of this application, please upload them to section 40.1 (e.g. tables, diagrams, pictures, spreadsheets, etc.).

12.3. Describe the statistical considerations for the study, how the sample size was determined, and how the results will be analyzed, if applicable. (HSC: refer to specific sections of the protocol/grant, if applicable)

Explain the statistical analyses you will use to test your hypotheses or determine if the study aims and objectives were achieved. If you are conducting a pilot study, state that it is a pilot study and explain how you will assess your findings. If applicable, explain how you determined the appropriate sample size to achieve statistical significance.

12.3.a. If needed, copy-and-paste any tables here and reference in the question above.

HSC only: If there are existing tables in the research proposal, protocol, or other study document that describe the statistical analysis, please refer to the page number or section of the document where the tables can be found, rather than copying and pasting them into the application.

If there are additional supporting documents that are necessary for the review of this application, please upload them to section 40.1 (e.g. tables, diagrams, pictures, spreadsheets, etc.).

14. Methods and Procedures – Retrospective Studies/Existing Data

14.1 Specify the dates of and number of records/specimens that will be used. Describe the method of collection for the records/specimens and how the data/specimens will be analyzed.

Describe the type of data and/or specimens you will collect and how you will analyze the data and/or specimens in your study. Please include answers to the following questions:

• What type of data, records, or specimens will you collect for your study?
• How many records or specimens will you collect?
• Where will you get the data/records? Is the data publicly available?
• How you will obtain the specimens? Were the specimens collected for standard medical diagnosis and care, or were the specimens collected as part of a previous research study?
• How will you analyze the data, records, or specimens?
• What time period will your sample of data, records, or specimens cover? The date of collection is important for the IRB to confirm that the data or specimens are all retrospective (existing at the time you submit your iStar application).

• Public Data: This study will use anonymous data sets obtained from the California Department of Motor Vehicles between the dates of 12/1/1968 and 11/30/1998. The data sets will include approximately 1,000,000 records. We will analyze changes in rates of motor vehicle accidents over the 30-year period.
• Hospital Medical Record Data: This study will use data abstracted from the medical records from approximately 950 patients with cystic fibrosis who were seen in the Pulmonology Clinic between August 1, 1999 and October 31, 2003. The data will be used to evaluate medication usage and hospitalization rates.

14.2 Does the retrospective/existing data involve records/specimens from deceased individuals?

The Common Rule (45 CFR 46) defines human subjects research as involving an interaction or intervention with a living person. Therefore, research involving data from people who are deceased (decedent data) is not considered human subjects research. However, Health Insurance Portability and Accountability Act (HIPAA) regulations apply to identified data from individuals who are either living or dead.

When decedent data is being used for research, HIPAA regulations require the institution to obtain the following from the investigators: (1) an indication that the use and disclosure of personal health information of descendents is sought solely for research and (2) an indication that the personal health information for which use or disclosure is sought is necessary for the research purposes.

The researcher may be required to provide documentation of the death of the individuals whose PHI is sought for the research study, if requested by the IRB.

14.3 (UPC Only) Attach the approval/permission letter to access existing data, if applicable. Do not include data use agreements here.

If you are accessing a data set that does not belong to you, please attach a letter granting you permission to use the data set.

15. Methods and Procedures – Banking of Specimens/Data

These questions appear because you checked the box for "Banking of Specimens/Data" in section #9.3. The banking of specimens/data refers to the creation of data and tissue banks (“repositories") to collect, store, and distribute human specimens and data for future research purposes. The repository activities involve three components: (1) the collection of tissue samples from investigators, (2) the storage and management of the tissues and data, and (3) distribution of tissue and data to other investigators for use in future research projects. The IRB at the institution where the repository is located must approve and maintain oversight of a protocol that: (a) specifies the conditions under which data and specimens may be accepted and shared with other researchers and (b) ensures adequate privacy protections for subjects contributing to the repository.

If your collecting specimens and data to be analyzed for use in the proposed study only and you will not be storing them in a repository for use in future research projects, please go back to question 9.3 and remove the check mark from the "Banking of Specimens/Data" box.

15.1 Specify the organization/site at which the data/specimens will be banked.

If specimens or data will be sent to and stored at a coordinating center or another institution to establish a repository, provide the name of that center or institution.  

15.1.1. Attach a copy of the IRB approval for the bank, if applicable.

If the repository is located at another institution or organization, attach a copy of the IRB approval letter for operation of the repository at that institution or organization.

15.2. If the specimens/data will be banked at USC or CHLA, please provide the IRB# for the banking/repository protocol in the space below.

If you are banking specimens/data at an existing repository at USC or CHLA, provide the IRB number for the repository protocol.

15.2.1. If IRB approval has not yet been sought, please attach the Standard Operating Procedures and forms that will be used for the bank.

If you are requesting IRB approval to establish and operate a repository, the IRB must review and approve procedures for operating and managing the repository. Please attach the following documents:

1. Standard Operating Procedures for the repository. The operating procedures and policies should include, but are not limited to, the following elements:
   • Purpose of the repository
   • Specimen and data collection procedures
   • Specimen and data storage/retention
   • Specimen derivation and processing
   • Specimen and data distribution
   • Obtaining informed consent
   • Procedures for protecting privacy and confidentiality (for example, anonymization of specimens/data, coding of specimens/data, encryption, limited access/secure storage)
   • Employee confidentiality measures and confidentiality agreement
   • Procedures for return of research results (if and under what conditions)
   • Repository oversight
   
   

2. Sample informed consents for subjects contributing to the repository

3. Sample agreements for investigators collecting tissues for the repository and for investigators receiving tissues from the repository. These agreements should address use of specimens/data, human subject protections, sharing of specimens with third parties, commercial use of specimens, biohazards, and indemnification.

4. A Certificate of Confidentiality, if needed. Certificates of Confidentiality are issued by the National Institutes of Health to protect identifiable research information from forced disclosure. Certificates of Confidentiality may be granted for studies collecting information that, if disclosed, could have adverse consequences for subjects or damage their financial standing, employability, insurability, or reputation. Certificates of Confidentiality are addressed in section #26.7. Additional information is available at the NIH Certificate of Confidentiality Kiosk web site.

For more information and guidance on repositories, visit the USC OPRS Human Specimens Guidance web page.

For additional information on repositories, please read the OHRP Guidance on Research Use of Stored Data or Tissues or contact your IRB office.

Deception may be appropriate for use in some behavioral research studies. Minor deception, such as withholding specific information to try to prevent bias in the results, can be acceptable if the subject is fully informed after participation. Major deception, such as leading subjects to believe they have committed a crime or have a disease, involves risks that must be clearly balanced by the benefits of the research.

• Misrepresenting the purposes of the research
• Making false statements as to the identity of the researcher(s)
• Making false promises to subjects
• Misleading explanations of equipment and procedures
• Using confederates
• Concealed observation

The use of deception imposes special responsibilities on the investigator and the IRB. The investigator must provide justification for the use of deception and explain why alternatives could not be used. When deception is used in the study, the investigator must ensure that subjects are debriefed (informed about the deception) as soon as possible. The IRB cannot approve a study that exposes subjects to greater than minimal risk if information considered material to their decision to participate is withheld. In addition, the IRB will not approve any study where deception involves a risk of physical injury or severe emotional discomfort.

16.1. Describe the information that will be withheld from, or misinformation that will be provided to subjects, and the justification.

Please describe the type of deception to be used in your study. Justify in detail why you need to use deception and explain why the research could not be done without deceiving the subjects. Explain what alternatives to deception were considered and why you judged them to be unacceptable alternatives in this study. Explain how the potential benefits of the research justify the use of deception.

16.2. Describe the plans for de-briefing subjects after their participation, if applicable.

De-briefing is informing the subjects about the deception used in the research. Explain how and when you will tell subjects about the deception.

16.3. Attach the debriefing statement that will be given or read to subjects, if applicable.

The Debriefing Statement could include the following:

1. The questions, hypotheses, and issues that motivated the research.
2. The background leading to the research question being studied.
3. The logic that underlies the study, including identification of experimental conditions and how they relate to the hypotheses.
4. An explanation of how the data gathered from that participant will be used to address the hypotheses.
5. A promise to keep participants informed of the results of the experiment. You can say, “If you would like to receive a report of this research when it is completed (or a summary of the findings), please contact (name) at (e-mail).”
6. An accessible reference for further reading. This reference must be found easily by students.

A medical device is any health care product that does not achieve it primary intended purposes by chemical action or by being metabolized. Medical devices range from simple tongue depressors and bandages to cardiac pacemakers, surgical lasers, imaging systems, and diagnostic products such as pregnancy test kits. If you are conducting a clinical investigation of a medical device, your study must comply with the Investigational Device Exemption (IDE) regulations at 21 CFR 812.

The regulations address three types of device studies:

1. Significant Risk Device Study

Significant risk (SR) devices present a potential serious risk to the health, safety, or welfare of a subject. A clinical study of an SR device must follow all the IDE regulations, and the sponsor of the SR device must obtain an approved IDE application from the FDA before any clinical investigations can begin. An IRB must review and confirm the sponsor’s assessment of the risk level before approving the study.

2. Nonsignificant Risk Device Study

Nonsignificant risk (NSR) devices do not meet the criteria for a significant risk device and must only meet the “abbreviated requirements” of the IDE regulations. The abbreviated requirements address product labeling and promotion, recordkeeping, study monitoring, and the need for IRB approval and informed consent. Studies of NSR devices do not require an approved IDE application, but the IRB must determine that the device represents a nonsignificant risk to subjects.

3. Exempt Device Study

Certain device studies are exempt from the IDE regulations. These include human studies of: (a) a legally marketed device when used in accordance with its labeling, (b) a diagnostic device that is not invasive, or (c) a device or combination of devices undergoing testing for consumer preference or modifications if the devices are legally marketed, the testing is not the purpose of determining safety and effectiveness, and the testing does not put human subjects at risk. Certain studies that are exempt from the IDE regulations may still require IRB approval.

A special type of medical device is the Humanitarian Use Device (HUD). An HUD is a device that is intended to benefit patients with rare conditions or diseases (affecting fewer than 4,000 people in the United States per year) and that is exempt from the effectiveness requirements of sections 514 and 515 of the act. The Office of Orphan Products Development determines if a device can be designated as an HUD. The FDA must approve a Humanitarian Device Exemption (HDE) application before the HUD can be marketed. The HDE application clears the HUD for marketing, and the use of the device does not constitute research. However, the IRB must approve the use of an HUD before it is administered to patients at that institution.

FDA Information Sheets - Frequently Asked Questions About Medical Devices
FDA Information Sheet - Significant and Nonsignificant Risk Device Studies
FDA Device Advice Web Site

If you don’t know the regulatory status of the device, contact the study sponsor or the device manufacturer. The study sponsor should be able to provide you with all the information and documents requested in this section.

Devices are exempt from the IDE regulations if they fall under of the three categories listed in question 18.1.4. A device can be legally marketed if the FDA determines that the device is safe and effective for its intended use and approves a Premarketing Approval application (PMA) submitted by the sponsor. Devices can also be legally marketed if the sponsor submits a premarket notification demonstrating that the device is substantially equivalent to an approved, marketed device and the FDA agrees with the sponsor’s assessment. This is known as a 510(k) premarket notification. The study sponsor or manufacturer of the device can provide you with this information.

18.1.5. If the device has a humanitarian device exemption (HDE), indicate the HDE number and attach the HUD document below.

18.1.5.1. Attach the HUD document.

18.1.6. If the device qualifies for an abbreviated IDE (nonsignificant risk devices), choose one of the following and attach the document below.

18.1.6.1. Attach documentation from the sponsor.

18.1.7. If the device requires an IDE (significant risk device), specify the IDE number and attach a copy of the FDA letter indicating approval when available.

18.1.7.1. Attach a copy of the FDA letter indicating approval.

18.1.8. Name of IDE Holder

18.2. Attach a copy of any Investigators Device Brochures for the devices listed above

18.3. Indicate where the investigational devices will be stored, how they will be secured, and how the inventory will be managed.

19.1. Attach copies of any scripts and/or questions that will be used to guide the interviews/focus groups.  

If you are conducting interviews or focus groups, please attach a document describing the planned content of the interview or session. This document could be a script for the focus group leader or a list of interview questions or discussion topics to be covered in the interview or session.

Interviews and focus groups should be conducted by persons who have the necessary training and expertise depending on the nature of the research, the topic of investigation, and the study population. Please provide the following information:

1. The names of the research team members who will be conducting the interviews and/or focus groups.
2. The specific academic degrees, qualifications, and/or training that qualify the team member to conduct the procedures.
3. The individual(s) conducting the interviews or focus groups must be listed as study personnel in question #2. These individuals must complete the CITI human subjects training course.

• For a study using a standardized, diagnostic, psychiatric interview with individuals who have a history of depression: James Smith, M.A. and Mary Jones, Ph.D. will conduct the study interviews. Mr. Smith is a graduate student in psychology and Dr. Jones is a licensed psychologist. They both have attended a workshop on the administration of the interview and have achieved inter-rater reliability. Both Mr. Smith and Dr. Jones have clinical experience working with patients with depression.
• For structured interviews with close-ended questions on the opinions of high school teachers regarding math curricula: The following graduate students from the School of Education will administer the interviews: James Smith, Mary Jones, and Betty Kim. The principal investigator has trained each of them on the administration of the interview.

Psychophysiology is a discipline that explores the interrelationships between physiological and psychological aspects of behavior. Common methods of psychophysiological testing include non-invasive physiological measures such as heart rate, skin conductance, functional MRI, and cortisol levels.  

20.1. List all of the measures/instruments that will be used for this study.

Please provide a clear description of the types of psychophysiological equipment, techniques, or instruments that will be used in the proposed study.

If you are using equipment or instruments for psychophysiological testing, attach illustrations, diagrams, and other information about the equipment here. Describe how the measures will be used. 

Psychophysiological measures should be conducted by persons who have the necessary training and expertise depending on the nature of the research tool, the topic of investigation, and the study population. Please provide the following information:

1. The names of the research team members who will be conducting the psychophysiological measures.
2. The specific academic degrees, qualifications, and/or training that qualify the team member to conduct the procedures.
3. The individual(s) will conduct the tests must be listed as study personnel in question #2. These individuals must complete the CITI human subjects training course.

The galvanic skin response measures will be conducted by two psychology graduate students, James Smith and Mary Jones, under the supervision of the Principal Investigator, John Flesh, Ph.D. Dr. Flesh has published extensively on the use of this technique.