Clinical Trials Administrative Start-Up Handbook

SECTION 4

General Information about Institutional Review Board (IRB) Review

Federal and state regulations and UW policy require that the use of human subjects in research be reviewed and approved by an Institutional Review Board. IRB responsibilities include weighing ethical issues, assessing potential benefits against risks, and assuring that subjects are recruited and consented appropriately. At the UW, with certain exceptions, the UW IRBs assume these responsibilities.  The UW IRBs are supported by staff in the Human Subjects Division (HSD) of the UW Office of Research.

Depending on several factors, your study may be reviewed by:

•  a UW IRB
•  an IRB at another institution
•  Western Institutional Review Board (WIRB)
•  the Cancer Consortium IRB

Information in this section of the Handbook will help investigators determine where to submit their IRB applications andwhat forms to complete.  If you have questions about the various arrangements and options for review, call the HSD at (206) 543-0098.

Determining Where Your Study Needs to be Reviewed

In order to determine which IRB will review your study, follow these steps:

1. Visit the UW HSD page that describes cooperative agreements with IRBs at affiliated institutions.
   
   To avoid duplication of effort, the UW has developed agreements with several local institutions whereby only one IRB review is necessary for collaborative research, and the HSD cooperative agreements page provides summary information about those agreements.  In almost all cases, the agreements are reciprocal, that is, the UW accepts their IRB's review and they accept ours.
   
   
2. If your study does not fall under a cooperative agreement, and if your study is an industry-sponsored clinical trial, consult the UW/WIRB FAQs to determine whether your study is eligible for review by WIRB.   Continue to check these FAQs, as they are continually updated.  Note that for industry-sponsored clinical trials, UW Cancer Consortium members may choose review either by the Cancer Consortium IRB (see #3. below) or by WIRB.
   
   Complete information about the UW-WIRB arrangement, including a process flow chart and the WIRB Fee Schedule, is available at the HSD Website. Additional information is included in this Section of the Handbook at If your study is reviewed by WIRB.
   
   
3. If you (the UW investigator) are a Cancer Consortium member, your cancer-related studies - either therapeutic or observational - will be reviewed by the Cancer Consortium IRB (CC-IRB) at the Fred Hutchinson Cancer Research Center (FHCRC). For industry-sponsored clinical trials, UW Cancer Consortium members may choose between review by the CC-IRB or by WIRB.  Other, non-cancer related studies by UW Cancer Consortium members will continue to be reviewed by the UW IRBs. 
   
   Additional information is included in this section of the Handbook at If your study is reviewed by the Cancer Consortium IRB.

Aside from the above “exceptional” arrangements, the UW IRBs are the IRBs of record for the following:

• All UW agencies (e.g., schools, departments, programs, clinics, UW Medical Center, Harborview Medical Center)
• Veteran's Affairs Puget Sound health Care System (VAPSHCS – Seattle and American Lake)
• Boise VA
• Seattle-King County Department of Public Health
• Puget Sound Blood Center

Information in this section of the Handbook will help investigators determine where to submit their IRB applications and what forms to complete.  If you have questions about the various arrangements and options for review, call the HSD at (206) 543-0098.

If Your Trial is Reviewed by the UW IRB

Beginning the UW review process:

To begin the review process, complete form UW 13-11.  Included with the form are instructions for completing and submitting it.  Also, see Best Practices for Completing the UW HSRC Application and Best Practices for Writing Consent Forms.

The HSD staff will screen your IRB application in the order received and will contact you if there are questions about the application. After you have answered all screening questions, HSD staff will assign the application to the next available IRB agenda. IRB meetings are held weekly and agendas are mailed to IRB members approximately one week prior to each meeting. After the IRB meeting, you will receive either a copy of the approved application or a letter from the IRB Chair outlining the additional information and revisions required by the IRB.  You will need to send a written response to the Chair's letter.  Your response will be put on the next bi-weekly available agenda of the IRB that originally reviewed your application.  Assuming that your response is satisfactory, the IRB will approve it with an assigned approval period (ordinarily one year).  Letters and other exchanges of information can be handled by campus mail, FAX, or email attachment. 

Sponsor requests for UW IRB membership lists:

A sponsor may ask for a membership list of the UW IRB that reviewed your trial. Such a request is usually based on the sponsor's misinterpretation of an FDA regulation requiring assurance by the sponsor that the trial will be conducted according to applicable FDA regulations. In response to such requests, the UW IRBs have developed a "Sponsor Assurance Letter" that can be found on the HSD Forms Web page (under "Commonly Used," hit "Browse All"). The letter explains why the HSRC membership list is not required and includes an FDA Information Sheet that specifically addresses this issue. You can copy the memorandum onto UW letterhead, send it to Karen Moe for signature, and then forward it and the FDA Information Sheet to sponsors who may require it.

The Federal Wide Assurance Number:

The UW has a Federal Wide Assurance (FWA) number on file with the Office for Human Research Protections (OHRP), an office within the Department of Health and Human Services which administers regulations concerning IRBs. You may need to know the FWA number when completing forms connected with your clinical trial. The University's FWA number is FWA00006878.

Recruiting research subjects at the UW:

The IRB will require information about your subject recruitment plans, including the text of recruitment tools such as advertisements, flyers, newspaper ads, and announcements placed on the Internet. For advice about writing recruitment advertisements and related issues, read Approaching Prospective Subjects on the HSD Website.

Faculty at the UW Health Sciences schools may post IRB-approved clinical trial descriptions on the UW Research Studies Seeking Volunteers Website. Follow the Instructions for posting studies on the Web site. Remember to include the study description template in your original submission to WIRB, as WIRB charges separately for each modification.

Paying research subjects:

Often, researchers wish to offer a small payment to human subjects for participating in studies. Payment is intended to reimburse subjects for time and inconvenience, not for risk. Payment should be appropriate to the trial's target population and should not be so high that it might be viewed as an undue inducement to participate. The UW IRBs will review your proposed payment level and method according to the Subject Compensation guidelines in the Human Subjects Manual. WIRB payment guidelines are explained in “A Guide for Investigators,” available at the WIRB Website on pages 19 and 31-32.

Generally speaking, subjects can be paid with cash, checks, or gift cards. The most convenient payment method will depend on the length of the trial and the amount you wish to pay subjects. Other considerations include whether you are comfortable having cash in your office and whether you can arrange for adequate security (UW police must inspect and approve your security arrangements if you expect to keep more than $100 in cash.)

Payment to research subjects must be arranged through the University of Washington Payables Administration Office. Consult the Payables Administration Office Website for detailed information about all payment methods .  This link includes complete descriptions of payment methods, advice about which of the methods might best fit your trial, links to required UW forms, information about IRS reporting requirements, and account reconciliation instructions.

Expediting the review process:

Respond as quickly as possible to the IRB's requests for information. Recent data show that investigators typically wait approximately one month (median, 2004) before responding to the HSRC.

Request that the UW IRB's correspondence to be faxed to you. Attach a request to your application and include the name and fax number of a person who is usually available by telephone and who is authorized to receive the investigator's confidential correspondence. When the correspondence is ready, the HSD staff will call that person and alert him/her to expect a faxed copy of the letter, to be followed by the original, mailed signature copy. If you do not request the fax, IRB correspondence will be sent via campus mail.

Best practices for completing the UW HSRC application:

• Read Common Human Subjects Application Problems on the HSD Website.
• Do not reformat Page 1 of the application. (For record-keeping purposes it is important for all Page 1 information to be available at a glance.)
• Obtain all necessary signatures on Page 1 of the application.
• Be sure to include (a) one copy of the trial protocol, and (b) one copy of available toxicity data and reports of animal and human studies (usually provided by the sponsor and called the “Investigators Notebook” or “Investigator's Brochure”).
• Provide copies of any proposed recruitment instruments, e.g., advertisements, brochures, text of announcements.
• Answer all of the questions in the application. If a question does not apply to your trial, write “does not apply”.
• Provide complete answers to the questions in the space provided on the IRB application form. Do not refer to the accompanying protocol or to a grant proposal.
• List all drugs (not just the investigational agent) to be administered according to trial protocol, e.g., anti-nausea drugs, eyedrops for eye examinations, topical anesthetics.
• Note carefully Item VII.F.3. of the application which asks “Who will be financially responsible for treatment of physical injuries resulting from study procedures?” If you are following a protocol written by the sponsor, using the sponsor's investigational product, it is the position of the UW that subjects and their third party payers should not be held financially responsible for the costs of treating adverse effects resulting from the properly performed, prescribed use of the test article or protocol. Please refer to the UW guidelines for compensation in clinical trials. Also, note the related Sample Consent Form for Clinical Trials language about costs of treating adverse effects.

Best practices for writing consent forms:

• If your trial will be reviewed by the UW IRBs, use the Sample Consent Form for Clinical Trials . Although this sample form is geared to industry-sponsored trials (usually reviewed by WIRB), it can be adapted to other similar studies of investigational agents. Embedded in this sample form are various risk statements for procedures commonly used in clinical trials. The UW risk statements are separately listed below for easy reference.
• Arterial puncture risks
• Confidentiality risks
• Drug risks
• ECG risks
• MRI risks
• Placebo risks
• Pregnancy risks
• Questionnaire risks
• Radiation risks
• Randomization risks
• Venipuncture risks
• Vision testing risks
• For other sample consent forms, go to the HSD Web site to view a comprehensive list of sample and special-situation consent forms, a checklist of consent form elements, and helpful hints about writing and submitting consent forms. As you read through the list of sample consent forms, note that under certain circumstances you might require more than one consent form. For example, under the Health Insurance Portability and Accountability Act (HIPAA), you must obtain research subjects' consent to use, create, or disclose health information about them. This consent is called “authorization.” To obtain authorization from subjects, you will need to append a University of Washington Standard HIPAA Consent Form to your approved “main” trial consent form and ask subjects to sign both forms.
• Go to the Consent/Assent Forms page at the HSD Web site. Be sure to note the “Additional Consent Form Information” near the bottom of the page.
• Write the consent form in simple, non-technical language – between the sixth and eighth grade reading level.
• Use short sentences and short words.
• Avoid technical language and professional jargon. If it is necessary to use technical terms, define the terms in simple language.
• Use the active rather than the passive voice.
• Do not write the forms in the first person cingular, e.g., “If I agree to participate in this study, I will have a chest x-ray.” Instead, use second or third person form of address.
• Include all elements of informed consent required by the FDA . Include relevant elements of informed consent from the UW IRB's "Consent Form Checklist" that is available on the HSD's Consent/Assent Form Web page. Note that all of these required elements are included, with sample wording, in the UW Clinical Trials Sample Consent Form .
• Include the flow sheet from the trial protocol. (This is not required, but is regarded by the UW IRBs as a good visual reference tool for subjects.) Here is an example of a study flow sheet .
• Do not overestimate benefits or underestimate risks, especially psycho-social risks.

Key UW contacts:

Visit the staff page at the Human Subjects Division Website for names   and contact information.

UW timeline:

Meetings are heal weekly. Individual committees meet bi-weekly. Applications are received, screened, and assigned continuously to the next available committee agenda. Call (206) 543-0098 for more information. If you want to be notified when your application is assigned to an IRB agenda, attach a request to your application and include the email address of the person to whom the notice should be sent.

UW HSRC Web site:

UW Human Subjects Division

If Your Trial is Reviewed by Western Institutional Review Board (WIRB)

Background:

Many industry-sponsored clinical trials conducted at or through the University of Washington can be reviewed and followed by Western Institutional Review Board (WIRB). The arrangement with WIRB became effective on June 8, 2005. WIRB's fee schedule is posted at the Human Subjects Division Web site. WIRB fees are paid by your trial's industry sponsor, via arrangements made through the Clinical Research Budget and Billing Office (CRBB).

Although your study will be reviewed by WIRB, other regulatory review and approvals must be done at the UW . Depending on your trial, examples of other reviews might include conflict of interest, Radiation Safety Committee, Institutional Biosafety Committee, and/or Implant and Investigational Device Committee. Although WIRB would prefer that you include the approvals from these other reviews in your IRB application, you may arrange to provide the approvals after the application has been submitted to WIRB.

Beginning the WIRB review process:

• Consult the UW HSD Web site to access specific instructions about working with WIRB. As stated at the HSD Web site, "If you are going to use WIRB for review, it is essential that you read all of the instructions posted here as well as the instructions at the WIRB Web site." Not following these instructions will cause unnecessary delays in the review of your application.
• Complete the WIRB Initial Review Submission form (note that an annotated version is also available from the linked page). Then follow, step-by-step, the Instructions in Applying for Human Subjects Review by Western Institutional Review Board (WIRB).  As stated in these instructions, you must complete and submit to the UW HSD the UW-WIRB Cover Sheet . WIRB cannot review your application without this form. The UW HSD will assign a UW IRB number to your application, sign the UW-WIRB cover sheet, and return it to you within one business day. You - not the HSD - are then required to forward the WIRB application (by US mail, FAX, or email attachment) to WIRB.  Consult this flow chart to view an illustration of the UW's part in the WIRB review process.
• Receive from WIRB via email: 1) confirmation that they have received your application and 2) a tracking number. You can use the tracking number to trace the status of your application by means of the WIRB's Internet tracking system.
• Receive information and/or questions about your application from WIRB, via the mode of correspondence you indicated on your application (FAX, email, or US mail).  When any screening questions have been answered, the application will be assigned to a review panel. Use your tracking number to view your application's panel review date - then, one day after the panel meeting, call WIRB (1-800-562-4789) to learn the results of the review. If the panel has questions, you will need to respond in writing. Your response will be put on the review panel's next available weekly agenda. Assuming that your response is satisfactory, your application will be approved and returned to you with an assigned approval period (ordinarily one year).

The WIRB Web site:

Western Institutional Review Board

WIRB's A Guide for Researchers is an eighty-two page manual that includes background information and instructions critical to a successful review by WIRB. It is likely that you will want to print a copy and/or keep the Web version easily at hand. If you print a copy, be sure periodically to check the electronic copy for updates.

WIRB's Web page also includes, in Web format at the "Investigator/SMO" tab, much of the same information available in A Guide for Researchers.

Answers to WIRB FAQs are available at the WIRB Web site.

Best Practices for working with WIRB:

• For multi-site protocols, call WIRB Client Services at 1-800-562-4789 to determine whether WIRB has previously reviewed and approved your trial's consent form for another site conducting the same trial. This frequently occurs. Choosing to use the previously approved consent form will expedite the review process. If you choose to use the previously approved form, omit the consent form from your application altogether. Using the previously approved form, WIRB staff will incorporate UW site-specific information for you.
• Consult the WIRB Investigator Handbook, A Guide for Researchers . This Guide is full of essential information. Note especially: Section 6., “Working with WIRB for IRB Review – An Overview,” and Section 7., “Materials Required for Initial Review.”
• Remember to include along with your original application any recruitment advertisements and/or study description templates for the UW Research Studies Seeking Volunteers Website . This is important because each modification to your trial carries an additional charge that will be billed to the trial's sponsor.
• If your trial qualifies for review by WIRB, be sure to submit any applicable special-situation UW consent forms/authorizations (HIPAA, SFI review, Material Transfer Agreements, etc.) along with your WIRB initial application packet. The Instructions at the UW HSD Web site include important information about these special situations.
• Consult the WIRB Website when answering WIRB application items (for example, items 8., 9., and 10.) about staffing levels and training .
• For an answer to Item 14e., “Medical Monitor Name,” call the sponsor. If a medical monitor has not been named, answer “Unknown.”
• Be specific when answering Item 24b, “What type of facility is this site?” WIRB is looking for more information than “University,” e.g. if your trial site is UWMC, answer “Hospital.” If your trial will be conducted at more than one site, name all sites, e.g., “Seattle Cancer Care Alliance” and “UWMC.”
• To Item 30. ("Are there laws governing medical research in your state/province?"), answer "HIPAA."  To Item 30.a. ("Have the laws governing research in your state/province changed in the past year?"), answer "No."
• Ask your trial's sponsor for advice in completing section V. "Billing Information."  WIRB will bill the sponsor directly. Remember that if the sponsor fails to pay the billed amounts, you will be responsible for the fees.
• Respond promptly to WIRB's screening and review. WIRB has a firm thirty-day non-response policy. If you do not respond to WIRB reviews or questions within thirty days, your application will be closed and withdrawn.

Best Practices for writing the WIRB consent form:

• If your trial is eligible for review by WIRB, use the UW WIRB Consent Template at the HSD Website .  Note that this consent form template was developed specifically for UW investigators and is not the same as the standard WIRB form that is posted on WIRB's Website.
• Consult the WIRB Investigator Handbook, A Guide for Researchers. Note especially the advice and information in Section 5.G (beginning on page 15 of the Guide), “The Consent Form.”  Also, consult the Informed Consent Process at the WIRB Website.

Key WIRB contacts:

Call 1-800-562-4789 or email clientservices@wirb.com

WIRB timeline:

WIRB panels meet weekly. Applications are received, screened, and assigned based on both the specialty required to review the protocol and on the next available panel meeting. New applications generally go to the panel the week following receipt. Complete applications and associated review materials must be received by WIRB at least six working days before the panels is scheduled to meet.

If Your Study is Reviewed by the Cancer Consortium IRB

The Cancer Consortium IRB Review Process

Since September 1, 2005, all new IRB applications from UW Cancer Consortium members need to be submitted to the Cancer Consortium IRB (CC-IRB) at the Fred Hutchinson Cancer Research Center . The CC-IRB will accept new applications from UW investigators for cancer-related studies - both therapeutic and observational. If you are not sure whether your study falls into one of those categories, call the CC-IRB Office at (207) 667-3220.

Complete information, including flow sharts, checklists, submission instructions, the CC-IRB application, and the UW/CC-IRB Coversheet and Review Authorization form can be found on the CC-IRB Website.  Note especially the information about Radiation Safety Committee review and Biosafety Committee review and remember that all grants and contracts will continue to be negotiated by the institution receiving the award. 

Cancer Consortium IRB Best Practices:

• Submit CC-IRB documents first to the Protocol Office, not to the CC-IRB.  The Protocol Office coordinates other reviews (e.g., for scientific merit) that must happen prior to the CC-IRB review.  After these prior reviews occur, the Protocol Office will submit your application to the CC-IRB.
• Submit CC-IRB documents to the Protocol Office prior to the IRB submission deadline.  Check with the Protocol Office (206) 667-4520 for timing.
• Keep checking the CC-IRB Website to make sure that you are using the most recent versions of all forms.
• Remember to submit industry-sponsored protocols to the Protocol Office for scientific review prior to submitting an application to Western Institutional Review Board (WIRB).