CHILDREN’S HOSPITAL & RESEARCH CENTER OAKLAND

Instructions for Protocol Submissions

Table of ContentsPage

Summary……………………………………………………………...... 2

Clinical & Translational Science Institute (CTSI)...... 2

Research Categories…………………………………………………………….. 3

Research in Foreign Countries………………………………………………...3

Industry Sponsored Research…………………………………………………. 4

Steps to Completing a Protocol Application……………………...... 5

Policies for Obtaining Informed Consent...... 6-8

Consent Form Instructions………………...... 9

List of Rights …………………………...... 10

Human Subjects Protections Online Training Certification...... 11-12

Contact Names and Telephone Numbers...... 13

What is a Research Protocol?

It is important that all applicants understand the basics of a research protocol to ensure that each applicant is capable of conducting high quality research, and to ensure the rights of human subjects are protected. The following is a brief overview of a research protocol.

A protocol is a document that describes the parameters of a research experiment in specific detail. IRB’s are often called upon to review a very broad range of biomedical and behavioral research. Consequently, the written protocol must be descriptive enough to facilitate the understanding of a reviewer of the protocol without leaving too many unanswered questions about how the research will be conducted. It is the investigator’s responsibility to provide the IRB with a satisfactory protocol.

The nature and degree of risks to human subjects will vary with the type of research. For example, a study that collects data by the use of surveys will have different implications than a study that involves the administration of an investigational drug or medical device. Protocol requirements and adherence to the protocol need to be addressed in a manner that optimizes and protects the rights of human research subjects.

All prospective studies conducted with either patients or the staff at Children’s Hospital & Research Center Oakland (CHRCO) are subject to review by both the Research Committee and the IRB. Exception: studies that have had peer review and approval, such as NIH grants, R01 funded studies,and clinical studies that are part of the Children’s Cancer Study Group (COG, CCG), or AIDS Clinical Trial Group (ACTG), do not have to be reviewed by the Research Committee, and will be submitted directly to the IRB for review.

All studies of existing data, e.g., chart reviews, and all studies using discarded blood, urine, sputum, or tissue samples must be submitted to the IRB, and if appropriate, reviewed by the Research Committee. Many of these studies will qualify for Exempt status under Category 4. If you believe the study is Exempt from continuing IRB review, please contact the IRB for confirmation, and submit a Claim ofExemption-Category 4 Formorfor all other categories, a Claim of Exemption Form.

All studies conducted at CHRCO must have a member of the medical staff, the professional staff, or Children’s Hospital Oakland Research Institute (CHORI) staff as either the principal investigator or as co-investigator. All studies conducted by principal investigators who are not members of the CHRCO staff must have at least one CHRCO co-investigator.

CLINICAL & tRANSLATIONAL SCIENCE INSTITUTE (ctsi)

The Clinical & Translational Science Institute (CTSI) at CHRCO is a satellite of the CTSI at UCSF. The CTSI is funded by the National Institutes of Health (NIH) to facilitate clinical research, particularly if it involves outpatient care. The NIH has strict guidelines for how CTSI resources can be used, so not all clinical studies can be eligible for support from the CTSI. All clinical investigators are encouraged to discuss their projects with Laurie Schumacher, Ph.D. and Paul Harmatz, M.D. to determine whether they are eligible for CTSI support. Studies which will be supported by the CTSI must be approved by the CHRCO Research Committee, the CHRCO IRB, and the UCSF CTSI Advisory Committee, in that order. Preparation of studies for presentation to the UCSF CTSI Advisory Committee is an involved process, which should be discussed with Laurie Schumacher, Ph.D. and Paul Harmatz, M.D.

Research Categories

Research studies at CHRCO are divided into three categories of review: 1) Exempt from further review, 2) Expedited review, and 3) Full Research Committee and/or Full Board IRB review. Assignment to one of the categories is at the discretion of the Chairs of the Research Committee and IRB.

Exempt studies must meet the criteria for one or more of the 6 categories of research, as outlined on the Claim of Exemption form. Examples are retrospective chart review when patient identifiers are not recorded by the investigator, analyses of unidentified data or biological samples, and anonymous surveys.

Studies that can be reviewed and approved by expedited review must meet the regulatory requirements of the expedited review procedure. The studies must be minimal risk. These studies are submitted to the Chairs of the Research Committee and the IRB for review, rather than to the entire Committee. The submission includes all the elements of a complete submission, including a budget and signatures by appropriate individuals.

All studies that do not meet the exempt or expedited review criteria will be reviewed by the full Research Committee and the IRB, except as noted above. If an investigator has any questions about whether a study requires Research Committee and/or IRB approval, the IRB staff should be contacted.

Research Funded by U.S. Government
in Foreign Countries

Research conducted in a foreign country is welcomed at both the Research Committee and the IRB at CHRCO. The human subjects involved in the research must be afforded the twin protections of review by an Institutional Review Board (IRB) and informed consent before human subjects may be enrolled in such studies.

Research in a foreign country may raise numerous issues including whether the individuals who are being enrolled understand the research, and have provided informed consent. In some countries, a village is viewed as the appropriate entity to provide consent, written signatures are looked upon with suspicion, and reading levels prevent individuals from understanding written informed consent documents. Investigators should become knowledgeable about the customs and traditions in countries where research is being conducted under their jurisdiction.

Investigators will be expected to provide a clear description of the consent process and how that process affords the required Human Subject Protections.

INDUSTRY SPONSORED RESEARCH

All research that is sponsored by private industry, involving a drug, device, or other product requires a final negotiated contract with the company. The contract must be ready and under review at the time of IRB review.

No research shall be conducted until the Technology Transfer Officer of CHORIhas finalized the agreement. There are several common issues to be aware of that arise in industry sponsored research contracts.

There must be a section that states the company will pay the costs of medical treatment for injuries caused by the study drug, devise, product or protocol.

There must be language that allows the investigator to publish the results of the study. The company cannot claim that the data or results of the study are confidential information, subject to their control.

Intellectual Property Clauses may need revision if the investigator has potential claims to the research.

The compensation must be related to the completed and approved budget.

There may be other specific issues with individual contracts that will have to be negotiated.

Process:

  1. Your contract review will be conducted by CHORI’s Director of Technology Transfer.
  1. You will be contacted as soon as the review is completed. Be prepared to discuss required changes with the company.
  1. Negotiating the contract can take place simultaneously with submission to the Research Committee and/or IRB, but the contract must be finalized prior to review by the IRB. Keep in mind that the consent will reflect certain contractual terms, particularly conflicts of interest, compensation for subject injury and reimbursement of subjects.

CHILDREN’S HOSPITAL OAKLAND

STEPS TO COMPLETING A PROTOCOL APPLICATION

STEP 1

If you are submitting an industry study you will first need to submit a copy of the contract to the Director of Technology Transfer for review. If changes to the contract are suggested, the principal investigator will be responsible for making those changes to bring the contract into compliance. All industry studies need to be reviewed by the Director of Technology Transferprior to signature. The contract must be under review before going to the IRB and your budget must be reviewed by the Vice President, Research Operations.

* Please be advised that all non-grant funded research contracts need to incorporate an IRB review fee in the budget. Please refer to the IRB Fee Scheduleandinclude this sum while in budget discussions.

STEP 2

Complete the Application for Study Review form, the Checklist – Requirements for Research Involving Children form, and the HIPPA Supplement form. It is important to fill out each section completely. Complete the Financial Disclosure form if your study is industry sponsored and a financial interest exists.

STEP 3

If applicable for your study, prepare consent form(s) and assent form using the CHRCO template. The forms are on the website: Consent and Assent. After you prepare your consent form(s) and assent form (if applicable) please submit them to the IRB staff for initial review, before making any copies.

STEP 4

If you are required to present your study to the Research Committee you may be asked to make changes to your consent form(s) or protocol before proceeding to the IRB meeting. Once these changes are complete your study will be added to the IRB agenda. The revised documents must be submitted electronically, with changes tracked. After the IRB meeting you will receive from the IRB office a complete list of the changes to make to your consent form(s) and/or other documents. If you have any questions or concerns you should contact the IRB office with your questions to get further clarification. After making the requested changes, please submit your revised documents to the IRB office for approval. The revised documents must be submitted electronically, with changes tracked.

STEP 5

Remember even though you have been through both the Research Committee and the IRB you do not have final permission to begin your study until you get an approval letter from the IRB, and stamped consent forms, if required. You must have a signed contract, if you have an industry sponsored study. You will be notified in 30 days if you have not submitted your study revisions to the IRB office. If the changes have not been made in an additional 30 days, your study will be withdrawnand you will need to resubmit your application package to the IRB.

INFORMED CONSENT

Policies for Obtaining Informed Consent

Nature of Informed Consent

If a person agrees to become a research participant, this must be documented by a signed consent form, unless the IRB has approved a waiver of consent or waiver of documentation of consent (see below). Informed consent requires that the researcher must be honest, straightforward, and compassionate in sharing information about the procedures to be undertaken. The participant must understand the information and be independent and free from coercion to be able to give autonomous, informed consent.

Consideration of Risk

In deciding whether CHRCO should support proposed research, the IRB considers the risk to the participating children and the possible benefits of the research. The review and approval of the consent form by the IRB helps to ensure that informed consent is appropriately obtained.

The IRB decides whether the proposed project places individual participants “at risk.” An individual is considered to be at risk if exposed to the possibilities of physical, psychological, or other harm. The Department of Health and Human Services (DHHS) requires the IRB to make a finding for each proposed research project. The hospital is legally required to follow the rules of DHHS and/or the Federal Drug Administration (FDA) for all research approved by the CHRCO IRB.

The classifications for approval of research involving minor subjects are as follows:

45 CFR §46.404, Minimal Risk: No greater than minimal risk to children is involved.

45 CFR §46.405, More than minimal risk with prospect of direct benefit: More than minimal risk to children is present but the intervention or procedure may result in direct benefit for the participant (e.g., a monitoring procedure that is likely to contribute to the participant’s well being.) In this classification, the risk is justified by the anticipated benefit to the participant, and the relation of the benefit to the risk is at least favorable to the participant as any presented by available alternative approaches.

45 CFR §46.406, More than minimal risk with no prospect of direct benefit: More than minimal risk (but only a minor increase over minimal risk) to children is presented by an intervention or procedure that does not hold out the prospect of direct benefit to the participant. Furthermore, the intervention or procedure should: (1) present experiences to participants that are reasonably commensurate with those in the actual or expected medical, psychological, social or educational situations, and (2) yield generalized knowledge about the participant’s disorder or condition which is of vital importance for the understanding or amelioration of the participant’s disorder or condition.

45 CFR §46.407, Exceptions: When the risk associated with research does not meet any of the above classifications, the IRB may refer the protocol to the Secretary of DHHS and/or the FDA Commissioner who, after consultation with a "panel of experts" and "after "opportunity for public review and comment," may issue an approval for the research, if it satisfies the following criteria: (1) the research presents a reasonable opportunity to further understanding, prevention, or alleviation of a serious problem affecting the health or welfare of children, and (2) the research will be conducted in accordance with sound ethical principles.

How to Obtain Consent

To give informed consent, the participant or the participant's parent or legal guardianmust have all the information relevant to the study before signing the consent form, and the process must include the following:

Personal Contact: The investigator (s) or his or her designate must provide complete and understandable explanations regarding the study and the participant's role. Questions from the participant and/orthe participant's parents or legal guardians must be answered completely and clearly.

Documentation: An Informed Consent Form must clearly state each of the elements of informed consent. The document serves as a reference for the participants and parents or guardians. Exceptions to this are only when the IRB has granted a partial or complete Waiver of Informed Consent (see below).

Agreement from a Minor

A child’s agreement to participate may be required, depending on the nature of the study and the age of the child.

Generally, if the child is seven or older, the child should be given a full explanation of the risks, benefits and procedure of the proposed research in a manner that is comprehensible to the child. If determined by the IRB, the investigator must provide a separate age-appropriate assent form to document the child’s agreement. This should be written in simple, clear language, keeping in mind the age of the reader. The information should be presented in the same sequence as presented in the consent form for the parent or guardian. Address the participant in the second person (you, your). The child’s assentform should be signed by the child. There should be no signature by the parent or guardian on this form, to foster a sense of autonomy for the child. If the child who is seven or older does not have the maturity to understand the nature of the research, then the IRB will consider the age, maturity, and psychological state of the participants in determining capability to assent. Please use the Assent Form template on the IRB website.

The assent of the child is not necessary when the IRB determines that:

The capability of some or all of the children is so limited that they cannot be reasonably consulted, or

If the intervention or procedure involved in the research holds out a prospect of an important direct benefit to the health or well-being of the child, and is available only in the context of the research; or

The IRB has waived the consent requirement because the research involves no more than minimal risk to the subjects, the waiver will not adversely affect the rights and welfare of the child, the research could not practicably be carried out without the waiver, and whenever appropriate, the child and his or her parent or guardian will be provided with additional pertinent information after participation has begun.

All consent and assent forms must include the date of the latest revision in the lower left corner of the first pageand must be identified in the top left corner of the first page, including the IRB #. At continuing review, even if there are no changes, the form date should be updated (the version date can remain if required).