OHSU Cancer Institute Coordinating Center Policies and Procedures

Coordinating Center

Policies and Procedures

Table of Contents

1. MULTI-CENTER TRIALS 2

2. RESPONSIBILITIES OF THE COORDINATING CENTER 3

2.1 Site Pre-Approval and Study Initiation 3

2.2 Protocol Monitoring 3

3. RESPONSIBILITY OF THE OHSU PRINCIPAL INVESTIGATOR 4

4. RESPONSIBILITIES OF THE AFFILIATE INVESTIGATORS 5

5. IRB APPROVAL 5

Continuing Review 6

6. CENTRAL REGISTRATION 6

7. STUDY RECORDS 7

7.1 Case Report Forms 7

7.2 Source Documentation 7

7.3 Regulatory Binder 8

7.4 Study Closure 8

7.5 Record Retention 8

8. DRUG ORDERING, ACCOUNTABILITY AND STORAGE 9

8.1 Storage of Study Drugs 9

8.2 Procedures for Study Drug Accountability 9

8.3 Study Drug Returns and Transfers 9

8.4 Verification of Compliance 10

9. WHO MAY ADMINISTER STUDY DRUG 10

10. CENTRAL REPORTING OF ADVERSE EVENTS 10

11. REPORTING PROTOCOL DEVIATIONS 11

12. DATA SAFETY AND MONITORING 11

APPENICES:

A. List of Source Documents

B. Regulatory Binder Checklist

C. PROCEDURE FOR ORDERING STUDY DRUG FOR MULTI-CENTER STUDIES

D. RETURN OF AGENTS FORM

1. MULTI-CENTER TRIALS

The OHSU Knight Cancer Institute (CI) recognizes the importance of research collaboration with affiliate investigators. These collaborations increase the accrual base and offer more clinical trial options to underserved populations.

The OHSU Knight CI expects all affiliate investigators to comply with appropriate regulatory, protocol, and data collection requirements. The OHSU Knight CI has developed this policy and procedure manual to provide standardization of research practices and consistency in coordinating center activities. These procedures should be followed when drafting an OHSU investigator initiated trial.

2. RESPONSIBILITIES OF THE COORDINATING CENTER

2.1 Site Pre-Approval and Study Initiation

· Confirm that each participating site is affiliated with a local IRB that has a Federal Wide Assurance (FWA) of compliance on file with the Office of Human Research Protections (OHRP), DHHS.

· Confirm that affiliate site physicians have provided all necessary investigator documents. The following documents must be submitted to the OHSU Knight CI in order to collaborate on OHSU clinical protocols:

o Current resume or CV (signed and dated)

o Current medical license number

o Signed FDA Form 1572 (http://ctep.cancer.gov/forms/index.html). Each affiliate PI will sign and submit a 1572 and list all sub investigators at the site.

o Certificate of completion of the NIH online training in the protection of human research subjects (http://phrp.nihtraining.com)

o Signed OHSU conflict of interest form for outside investigators practicing at

institutions without a CoIR (http://www.ohsu.edu/research/rda/forms.shtml#coir)

· Confirm that a fully executed collaborative sub-contract is in place prior to registration of the first subject.

· Confirm that all sites are using the correct version of the OHSU protocol. The protocol must not be rewritten or modified by anyone other than the OHSU Principal Investigator.

· Confirm that the protocol and informed consent form have local IRB approval at each site prior to registration of the first subject.

· Confirm that the affiliate site has procedures in place for receipt and storage of study drug.

· Collect lab certification (if applicable) and lab normals for affiliate sites.

· Determine if the affiliate site has a Data Safety and Monitoring Plan (DSMP) and, if so, obtain a copy of the plan.

· Maintain documentation of all affiliate sites IRB approvals for protocols, continuing reviews, and all approved consents in regulatory binder.

2.2 Protocol Monitoring

· Providing centralized subject registration. The data will be recorded in the Clinical Research Management (CRM) database at OHSU Knight CI.

· Preparing all study data for review by the OHSU PI. Case Report Forms (CRF) will be in a standardized format. Protocol specific CRF will be provided, and the schedule for submitting them to the CC will be stated in each protocol. If not specified, the OHSU study coordinator will provide CRF submission instructions at site initiation (i.e. monthly or per cycle).

· Maintaining documentation for all serious adverse event (SAE) reports. The CC will submit SAE and/or unanticipated problem (UP) reports to the OHSU PI and UP reports to OHSU IRB for continuing review.

· The CC will prepare Quarterly Summary Reports of SAEs from all sites. The report will include the enrollment numbers. The Quarterly Summary Report will be submitted to CRM, OHSU IRB and each affiliate investigator for submission to their local IRB. SAE reports will be reported to affiliate sites in real-time if indicated for subject safety.

· Assuring that relevant IRB correspondence and study status changes are communicated to all affiliate sites.

· Performing audits in accordance with the sub site’s Data and Safety Monitoring Plan (DSMP) or as per Section 12 of this document if sites do not have their own DSMP.

3. RESPONSIBILITY OF THE OHSU PRINCIPAL INVESTIGATOR

The OHSU Principal Investigator (PI) is the physician who assumes full responsibility for the integrity of the research data. The PI is responsible to see that the protocol is followed, subject safety not compromised, and the data is accurate. Specific PI responsibilities are:

· Coordinating all protocol activities with the assistance of the PI’s assigned study team

· Coordinating the design and development of the protocol document and informed consent form

· Providing oversight of study conduct, data quality and accuracy

· Identifying any necessary changes in the protocol and the informed consent documents and submitting them as protocol amendments to the OHSU IRB and providing copies to affiliate sites to submit to their local IRBs

· Monitoring protocol progress and ensuring that affiliate investigators comply with their reporting responsibilities

· Reviewing study data to ensure protocol compliance

· Reviewing all serious adverse events received from affiliate sites as well as the CC to assure safety of the subjects

· Initiating appropriate actions when subject safety is at risk

· Monitoring accrual to the study and stopping the study when the requirements of the study design have been fulfilled

· Submitting data to the biostatistician for study analysis, and leading the research team in preparation of reports and publications.

Additional Responsibilities of Principal Investigators who Sponsor Investigational

New Drug Applications

· Amendments – The PI will submit to the FDA any protocol amendment that significantly affects the safety of subjects, the scope of the investigation or the scientific quality of the study or the addition of a new investigator or sub site as per section 312.30 of Title 21 of the Code of Federal Regulations (CFA).

· Serious Adverse Experiences – The PI will report to the FDA any unexpected fatal or life-threatening adverse experience associated with the use of study drug(s) by telephone or fax no later than 7 calendar days after initial receipt of the information; they will also report to FDA in writing any adverse experience associated with use of the study drug(s) that is both serious and unexpected no later than 15 calendar days after initial receipt of the information as per section 312.32 of the CFR.

· Annual Reports - The PI will submit annual reports to the FDA as per section 312.33 of the FDA CFR Title 21 which will include a summary of study status, number of subjects enrolled as summary of all IND safety reported during the past year.

4. RESPONSIBILITIES OF THE AFFILIATE INVESTIGATORS

An affiliate investigator of the OHSU Knight CI is a physician who participates in clinical trials conducted by the OHSU Knight CI. Affiliate investigators must be board certified in radiation, surgical or medical oncology and must have a certificate of completion of NIH research training (http://phrp.nihtraining.com.)

Affiliate investigators are responsible for:

· Submitting to OHSU CC all relevant documents and IRB approvals prior to enrolling a patient

· Submitting to OHSU CC all local IRB approvals for protocol modifications during the course of the study

· Complying with all local, state and federal regulatory requirements

· Following CC policies and procedures for conducting OHSU clinical trials. Sub sites are encouraged to share internal SOPs with OHSU when in conflict with OHSU CC policies and procedures

· Accruing a minimum number of subjects agreed upon to meet protocol objectives

· Informing subjects or their representatives that agents are being used for investigational purposes and will obtain the written consent of the subjects or their authorized representatives, using the most recently IRB-approved informed consent form

· Documenting subject eligibility and maintaining accurate case histories designed to record all observations and other data pertinent to each subject

· Submitting accurate and complete data to OHSU in a timely manner

· Ensuring that OHSU is listed in study-related HIPAA documents

· Ensuring study drug records are maintained

· Reporting all SAEs to the OHSU CC and to their own IRB according to protocol and institutional guidelines

· Preparing for audits by making available all source documents, research records, IRB approval documents, drug accountability record forms, subject registration lists, screening logs, and other documents as requested prior to the audit date.

5. IRB APPROVAL

Research involving human subjects must meet the requirements of the federal regulations for human subjects protection as detailed in the Code of Federal Regulations (CFR) sections 45, 46, 21, 50 and 56 (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm). An IRB must review and approve human subject research activities to ensure compliance with all applicable local, state, and federal policies and regulations.

Protocols and informed consents will undergo review and approval at the CRRC and the OHSU IRB prior to distribution to the affiliate sites. Following study document distribution, the affiliate site will submit a draft consent form to the CC for review by the study PI and study team. Upon OHSU PI approval of draft consent the affiliate site will submit the protocol, the consent form and other study documents to their local IRB. Any consent form revisions requested by the local IRB must be approved by OHSU PI prior to final local IRB approval.

Evidence of local IRB approval and copies of approved consent forms must be submitted to the CC prior to enrollment of any subjects. CC study coordinators will submit sub site IRB approval letters and informed consent documents to OHSU IRB. Sub sites may enroll subjects while OHSU IRB reviews the sub site approval documents as long as subcontracts are fully executed.

In order to decrease barriers to recruiting minorities to clinical trials, foreign-language short informed consent forms may be used for subjects who do not understand English. A medical interpreter must orally translate the IRB approved English informed consent document and the subject must sign the short consent form stating that the consent form was understood. Templates of these forms are available in Spanish, Russian, Serbo-Croatian, German, Chinese, Vietnamese and Korean (http://www.ohsu.edu/ra/forms.shtml#hsf). Affiliate sites may use these documents if approved at their local IRB. If the subject does not understand these languages, the affiliate site should contact their local IRB for assistance.

Continuing Review

Federal Regulations require that research involving human subjects be reviewed annually. The purpose of this process is to review an entire study and determine that the anticipated risks and benefits are reflected in the actual experience of subjects, and that the safeguards in place at the time of original approval are, in fact, adequate to ensure the safety of subjects.

All participating institutions must document annual IRB review of the protocol and an approval letter and copy of the approved informed consent form must be provided to OHSU CC. Sub site annual review approval memos and consent forms are to be included in the OHSU IRB continuing review packet.

In addition to initial and continuing IRB approvals, all amendments and revisions to protocols must be reviewed and approved by the CRRC, the OHSU-IRB, and each site’s local IRB. No revisions will be implemented at the affiliate institutions without the prior approval of the CRRC, OHSU-IRB and the local IRB.

6. CENTRAL REGISTRATION

Central registration is used for tracking study accrual, checking eligibility and monitoring adequate participation of women and minorities. Subject registration will be conducted through the coordinating center at the OHSU Knight CI. The investigator at the affiliate site will identify eligible subjects. Registration will include a minimum of the following:

· A completed Central Registration Form.

· A completed Eligibility Checklist signed by the investigator.

· A copy of the most recently IRB-approved, signed informed consent form.

These documents must be faxed to the CC staff. The OHSU Knight CI CC will verify completeness of documents and enter the registration information in the Surveyor database. Affiliate sites will be requested to fax source documentation to OHSU in order to confirm eligibility.

Each site must maintain a log of all subjects who sign informed consents. The log must also document an explanation for exclusion due to screen failure. Subjects who are enrolled on study will be assigned a site and protocol specific subject number. Participating sites are required to retain, in a confidential manner, sufficient information on each subject so that the subject may be contacted should the need arise.

7. STUDY RECORDS

7.1 Case Report Forms

The investigator is required to complete case report forms (CRF) designed to record all observations and data pertinent to the investigation of each individual treated with the drug or employed as a control in the study. Standardized CRF will be provided for recording all data from each subject. It is the responsibility of the affiliate investigator to ensure that these CRF are properly completed and transmitted to the CC in a timely manner.

Affiliate sites will transmit CRF as clinical outcome data in the following manner:

· All information requested on the CRF must be provided. Any omissions require explanation

· Only the protocol specific subject ID number or subject initials must appear on all CRF to ensure subject confidentiality

· CRF must be typewritten or printed legibly using black ballpoint pen to ensure legibility of photocopied pages

· Corrections are to be made with a single line through the error, then initialed and dated.

· The investigator must sign the designated pages to attest that the CRF is accurate and complete

· Signed and completed CRF must be submitted to the CC electronically or via fax (503-494-3224) within 30 days of the subject’s visit or completion of a cycle or as specified by the protocol. If web-based CRF are used, data should be entered into the database within 30 days of the subject’s visit. The affiliate site must keep printed copies of the electronic CRF in the subject’s research file.

7.2 Source Documentation

All data recorded in the CRF must be traceable to the subject's source documentation. Source documents are the original records of subject information (see Appendix A for examples) and contain all the information related to a subject's clinical protocol treatment. An investigator is required to prepare and maintain adequate and accurate source documentation, to record all observations and verify the integrity of the study data, to confirm subject eligibility, and to assure that protocol procedures were followed. If an outside physician/institution other than the responsible study investigator treats a subject, it is the responsibility of the investigator to obtain the medical records for those visits.