Investigator Handbook to Human Research Activities. South Shore Hospital

Transcription

1 Investigator Handbook to Human Research Activities South Shore Hospital 1

2 INVESTIGATOR HANDBOOK CONTENTS WHO IS INVOLVED IN RESEARCH Principal Investigator... 6 Site PI 6 Co-investigators 6 Biostatistician 6 Research Nurse.. 6 Study Coordinator.. 6 Scientific Review 6 Sponsored Research 6 Letter of Assurance from the IRB.. 7 WHAT ARE THE REQUIREMENTS Required Training.. 7 Refresher Training. 7 Certification... 7 Investigator Responsibilities... 8 SUBMITTING TO THE IRB Submitting a Study for Review.. 8 Not Human Subject Research 8 Exempt Research... 8 Expedited Research 9 Convened IRB Review (Full Board). 9 WHAT IS REQUIRED WITH AN INITIAL SUBMISSION Initial Review. 9 New Research Application 9 Elements of the Form. 9 Compensation 11 Informed Consent.. 12 Legally Authorized Representatives.. 12 Participants Unable to Read Non-English Speaking Participants Assent. 15 Waiver or Alteration of Consent 15 FDA Form Clinicaltrials.gov 16 WRITING A RESEARCH PROTOCOL.. 17 Research Tools Advertisements.. 17 Recruitment Letters/Phone Scripts/ s 18 FINANCIAL DISCLOSURE BY INVESTIGATORS 18 2

3 CONTINUING REVIEW STUDY CLOSURE RESEARCH RECORDS. 20 MODIFICATIONS TO PREVIOUSLY APPROVED RESEARCH 20 Exceptions.. 23 REVIEW OUTCOMES PROBLEM REPORTING Unanticipated Problems Involving Risks to Participants or Others Serious Adverse Event (SAE) Reporting Policy...22 IND/IDE Safety Reporting Form PRIVACY AND CONFIDENTALITY Health Insurance Portability and Accountability Act (HIPAA) 23 What Constitutes PHI Minimum Necessary.. 25 De-Identified Limited Data Set Data Use Agreement Accounting of Disclosures.. 26 WHAT SERVICES ARE AVAILABLE TO INVESTIGATORS Submission Assistance Monitoring and Audit Preparation. 27 Routine Quality Assurance Review Directed Audits.. 27 Regulatory Binder.. 27 INVESTIGATIONAL STUDY DRUGS Use of Investigational Drugs and/or Investigational Devices 28 Investigator-initiated/IND or IDE Holder Reporting Requirements. 29 Sponsor IND Reporting Requirements.. 29 IND Protocol Amendments (21 CFR ) New Protocol(s). 29 Changes in Existing Protocols Content and Format of an IND Protocol Amendment IND Safety Reports for Investigator-Held INDs (21 CFR ) Review of Safety Information 30 IND Safety Reports 31 Telephone and Facsimile Transmission Safety Reports 31 Reporting format or frequency Marketed Drug Follow-up Action to an IND Safety Report

4 IND Annual Report (21 CFR ) 32 Withdrawal of an IND Application (21 CFR ) General Responsibilities of the Sponsor-Investigator 33 Selecting Investigators Control of Drug.. 34 Review of Ongoing Investigations (21 CFR ) 34 FDA Inspection.. 34 Treatment IND (Single Patient IND). 34 Emergency Use.. 35 MEDICAL DEVICES. 36 Significant Risk.. 37 Non Significant Risk. 37 APPENDIX A: Additional Requirements for FDA-Regulated Research APPENDIX B: Additional Requirements for Clinical Trials (ICH-GCP) APPENDIX C: Research Categories 47 APPENDIX D: Glossary of Terms

5 The Purpose of This Manual The Investigator manual is designed to guide investigators and staff through policies and procedures related to conducting human subject research at South Shore Hospital. Specific policies and procedures are available for review online in Lotus Notes in Policies and Procedures. Human Research Protection Program The mission of South Shore Hospital s Human Research Protection Program Plan (HRPP) is to protect the rights and welfare of subjects involved in Human Research that is conducted or overseen by SSH. The HRPP aims to promote a culture of compliance with the highest legal and ethical standards for the conduct of human research. Several departments within South Shore Hospital contribute to the functioning of the HRPP. Institutional Review Board The SSH IRB is the IRB of record for the SSH. The IRB reviews all research involving human subjects and have the authority to approve, require modifications in, or disapprove all research activities, including proposed changes in previously approved human subject research. Clinical Research Program The Clinical Research Program (CRP) at SSH is responsible for promoting good science and the protection of the rights and welfare of human subject participants. The mission is to promote, foster, and sustain the highest quality of clinical research at South Shore Hospital. To fulfill this mission, the CRP supports investigators interested in conducting research from application to publication. Services include assistance with preparing IRB submission documents, assessing infrastructure needs, identifying resources and coordinating services, negotiating budgets/contracts, training of staff, and assuring compliance with federal and institutional policies. For more information please call (781) Investigator and Study Staff Complaints When investigators and their staffs have suggestions or complaints regarding the human research protections program they are encouraged to contact one or more of the following individuals: Senior Vice President/Chief Medical Officer IRB Chair and/or Co-chair Director or the IRB Assistant of the Office of Research Office of the Clinical Research Program Division Chief President/Chief Executive Officer 5

6 WHO IS INVOLVED IN RESEARCH Principal Investigator The Principal Investigator must be a South Shore Hospital employee. Additionally, the PI is generally required to hold an advanced degree. SSH employed RNs operating within the scope of their practice as defined by the board of registration under which their licensure is covered may serve as PI with approval from the Staff Nurse Research Scientist and the approval of the Chief Nursing Officer. All PIs must have the appropriate level of authority and responsibility to direct the study. If these criteria are not met, a researcher may request an exception be made. Site PI For multi center trials, each participating institution will have a designated site PI who is responsible for the conduct of the trial at that particular institution. The site PI is responsible for collaborating with the overall PI to ensure appropriate clinical conduct, including reporting of serious adverse events (SAEs) and unanticipated problems. Collaborating Investigators (Co-investigators) Co-investigators are invited by the overall PI to participate in the research trial. They, too, must ensure appropriate clinical conduct by adhering to and performing the trialspecific procedures on behalf of the overall PI. Biostatistician A biostatistician collaborates on various aspects of protocol development and reporting. He or she works closely with the team to ensure the relevance and appropriateness of statistics generated for the trial. For SSH trials, the biostatistician will provide a design appropriate to the endpoints specified by the overall PI. Research Nurse The research nurse manages the day-to-day operations of the clinical trial, under the auspices of the overall PI. Study Coordinator The Study Coordinator is responsible for maintaining research subject records, abstracting data, and completing the case report forms (CRFs) supplied by Clinical Research Program (CRP) or the sponsor. Additional responsibilities may be assigned. Scientific Review Scientific review is performed by individual members of the IRB selected to carry out the scientific review of proposed research prior to IRB review. Sponsored Research Research with funding from an outside sponsor South Shore Hospital will have a contract or written agreement with the sponsor. The Clinical Research Program staff may assist the investigator and department chairs with budget revisions to ensure budgets are adequate. 6

7 It is recommended, but not required that contracts be finalized prior to IRB review and approval. Investigators may not begin research without a fully executed contract in place. Letter of Assurance from the IRB Many industry sponsors will request a roster of the IRB members. The Office of Research does not provide this list. Instead, the Office of Research provides a letter stating that the hospital is in compliance with all Massachusetts, HHS, and FDA regulations governing research on human subjects. WHAT ARE THE REQUIREMENTS Required Training All principal investigators must review the Investigator Responsibilities Policy and the SSH Human Research Protection Plan (HRPP). All Principal investigators are required to complete human subject protection training through the CITI program online. All investigators, research staff, and others who are required involved in the design, conduct, or reporting of Human Research are required to complete the CITI program online prior to initiating a study. The specific course required depends on the function of the registrant. Individuals who overlap two areas should complete Group 1. It is the Principal Investigator's responsibility to ensure all staff members have current training. Register to take the CITI course at Principal investigators with public health service (PHS) funding are also required to complete the Conflict of Interest training through the CITI program online. Failure to complete the required training will delay approval. For questions regarding the required human subject protections training, please contact the Office of Research at (781) Refresher Training Completion of a refresher course is required every three years. Individuals must complete the CITI Refresher course by their three-year anniversary. Subsequent recertification is required within three years of the previous re-certification anniversary. As a courtesy, the Office of Research sends reminder notices to individuals 30 days prior to the anniversary/expiration date. Lack of re-certification training by an individual listed on the protocol may result in removal from the study for that specific individual. Research staff will be re-instated once they complete the CITI refresher course. Certification The Office of Research receives automatic electronic notification from the CITI program when a course is completed through South Shore Hospital. This information is added to the SSH training database. If you need official documentation of human subjects training for grant purposes, please contact the Office of Research. 7

8 Investigator Responsibilities The PI is responsible for: Conducting the study in accordance with the relevant, current protocol and only making changes to the protocol after notifying the sponsor (if applicable) and the IRB, except when necessary to protect the safety, rights, or welfare of subjects Conducting the trial in accordance with the investigational plan, institutional policies, and all applicable regulations Personally conducting or supervising the trial Informing trial subjects that the drugs/devices are being used for investigational purposes and ensuring that the requirements relating to obtaining informed consent and IRB review are met Reporting to the sponsor and the IRB any adverse events (AEs) that occur in the course of the trial Reading and understanding the information in the investigator s brochure, including the potential risks and side effects of the drugs/devices Ensuring that all associates, colleagues, and employees assisting in the conduct of the trial are informed about their obligations in meeting these commitments Maintaining adequate and accurate records in accordance with all regulations and requirements and making those records available for inspection Maintaining a record of accreditation for all laboratories used during the trial SUBMITTING TO THE IRB Submitting a Study for Review Submissions should be sent to: South Shore Hospital Office of Research 55 Fogg Road, Mail Box 26 South Weymouth, MA The review process will begin when the Office of Research receives the complete submission package. Incomplete submissions will not be considered until complete. Not Human Subject Research Activities that do not meet the definition of Human Research do not require IRB oversight. Contact the Office of Research with any questions about whether or not the activity is human research Exempt Research Certain categories of research may be exempt from Institutional Review Board (IRB) review and informed consent requirements under the Federal Policy. The IRB is the appropriate entity to make a determination as to whether an activity is exempt. An investigator does not have the authority to make a determination that his/her study is exempt. Studies deemed exempt do not require continuing review. See appendix C: Research Categories Submit the form: Exemption Request 8

9 Expedited Research Certain categories of non exempt research may quality for review using the expedited procedure. These studies are reviewed on a rolling basis and do not require review by the convened board. See appendix C: Research Categories Submit the form: New Research Application Submit additional documents according to the submission checklist Convened IRB Review (Full Board) Non exempt research that does not qualify for expedited review must be reviewed by the convened IRB. Greater than minimal risk studies require full board review. The convened IRB meets every other month. Follow the submission deadlines to ensure timely review. Submit the form: New Research Application Submit additional documents according to the submission checklist WHAT IS REQUIRED WITH AN INITIAL SUBMISSION Initial Review The IRB must review and approve all Human subject research prior to implementation. Submit the form: New Research Application. Additional documents may include protocol, consent documents, Financial Conflict of Interest Form, Research tools, Advertisements, Grant Application, Sponsor protocol, study instruments, CV. Refer to the submission requirements checklist New Research Application Submit this form for new research proposals that involve human subjects, including clinical trials, social or behavioral research, use of human material or tissue, or medical record review Elements of the Form: SSH IRB# - This number is assigned by the office of research Protocol Title - Enter the complete protocol title. Do not use nicknames. Sponsor/Funding Source List all external funding. SSH Principal Investigator/Degree(s) Include the name, degree, and contact information for the SSH PI with responsibility for the conduct of human subject research. Other research team members List all people involved in human subject research. 1. Purpose of Study: Provide a brief description including aims, objectives, and hypotheses. 2. Background and Significance: Provide preliminary data and review of current literature to support aims of research. 9

10 3. Design: Describe study design, e.g., observational (retrospective or prospective cohort, cross-sectional, case-control) or clinical trial (randomized/non-randomized, blinded/unblinded). 4. Inclusion/Exclusion Criteria for Participants: Define target population and projected accrual. Explain justification for using any vulnerable populations. Vulnerable Populations Additional protections are required for certain populations including children, pregnant women, human fetuses, neonates, and prisoners. SSH does not conduct research that involves prisoners as participants. In the event that a research participant is incarcerated, the investigator must report to the Office of Research as soon as possible using the problem reporting form. If a subject becomes a prisoner while enrolled in a research study that was not reviewed according to Subpart C: Confirm that the subject meets the definition of a prisoner. Decide whether it is in the best interests of the subject to remain in the study or to terminate enrollment. Decide whether it is feasible for the subject to remain in the study. Determine whether Subpart C applies. o If Subpart C applies: SSH will find an IRB that can review the study. Note: If a subject is incarcerated temporarily while enrolled in a study and the temporary incarceration has no effect on the study, the investigator may keep the subject enrolled. 5. Recruitment of Participants: Describe how subjects will be identified and recruited. Identify who will recruit participants. Referring physicians who have been provided with general information about the trial may inform their patients that the trial is available and provide the patients with contact information to learn more about the trial and whether they might be eligible. However, the referring physician cannot check eligibility or obtain consent. 6. Resources available to conduct the human research: a) Justify that there is adequate time for the researchers to conduct and complete the research (i.e. what amount of time will be used to conduct the study) b) Qualifications of study staff (Confirm all staff have the skills and training to conduct this study) c) Describe the facilities where the research will take place (specify departments or locations) d) Describe the potential for recruiting of the necessary number of participants 10

11 e) Availability of medical and/or psychosocial resources that participants may need as a consequence of the research (when applicable, the protocol should include plans for referrals) 7. Study Procedures: Detail all procedures to be performed, clearly differentiating between research procedures and procedures being performed already for diagnostic or treatment purposes. Indicate where procedures will be performed, who will be performing them, and how investigator/research team will be trained to participate in research. 8. Risks and Benefits: Identify, evaluate, and describe all risks and potential benefits. Explain how risks will be minimized and likelihood of benefits maximized. 9. Privacy: Describe steps to protect participants privacy interests (a person s desire to control access of others to themselves). 10. Confidentiality: Describe steps to limit dissemination of identifiable data: Explain how data will be coded and stored. If patient identifiers are to be used, explain how this information will be protected. 11. Compensation and Cost for Subjects: If applicable, describe compensation or reimbursement and provisions made to avoid out-of-pocket expenses for research subjects. Provide amount and schedule of all payments. Compensation o The amount and schedule of all payments should be presented to the IRB at the time of initial review and should be set forth in the informed consent document. o While the entire payment should not be contingent upon completion of the entire study, payment of a small proportion as an incentive for completion of the study is acceptable. The amount paid as a bonus for completion is reasonable and not so large as to unduly induce subjects to stay in the study when they would otherwise have withdrawn. o The IRB recommends the following as guidance to investigators: 1. When offered, incentives should generally not exceed $20-$25 per hour or $200-$250 per day, whichever is less. 2. The amount should be calculated based on the incremental time that study volunteers spend for research purposes. 3. Incentives may be offered to patient-subjects as well as to healthy volunteers. 4. Incentives must be described in any advertisements and in the consent form. 5. In addition to the incentives described above, remuneration for parking, meals, and other expenses incurred due to participation in a trial is appropriate for all study subjects. 11

12 12. Informed Consent: a) Identify the person who will conduct the consent interview. b) Identify the person who will provide consent or permission. c) Describe any waiting period between informing the prospective subject and obtaining the consent. d) Describe the steps taken to minimize the possibility of coercion or undue influence. e) Identify the language used by those obtaining consent and the language understood by the prospective subject or the legally authorized representative. f) Describe the information to be communicated to the prospective subject or the legally authorized representative. An investigator is required to obtain the legally effective informed consent of the subject or the subject's legally authorized representative, unless: The research is exempt The IRB finds and documents that informed consent can be waived The IRB finds and documents that the research meets the requirements of the HHS Secretarial Waiver that permits a waiver of the general requirements for obtaining informed consent in a limited class of research in emergency settings Informed Consent Investigators are required to use the most current informed consent document template. The IRB will affix the approval and expiration dates to all approved informed consent documents and will stipulate that copies of these approved, dated documents must be used when obtaining consent. The participant must be given sufficient time to read the consent document ask questions about participating in research. Requirements for customary (long form) consent documents: 1. The IRB approved consent document is used in the field 2. The participant or legally authorized representative signs and dates and consent document 3. The individual obtaining consent signs and dates the consent document 4. When required by the IRB, the participant of representative signature is to be witnessed by an individual who signs and dates the consent document 5. For participants who cannot read and when required by the IRB or sponsor, a witness to the oral presentation signs and dates the consent document. Legally Authorized Representatives For subjects who cannot consent for themselves (such as decisionally impaired) a legally authorized representative (LAR) must consent on their behalf. 1. The investigator must confirm that the person providing informed consent on behalf of the participant is qualified to serve as the subject's legally authorized representative 12

13 a. If a protocol targets subjects for enrollment, all of whom would be expected to have diminished decision making capacity (such as people with moderate to severe dementia), the study must require that consent be obtained from the subject s legally authorized representative (LAR). This person may act on behalf of the subject for consent purposes. b. A subject must have the right not to participate or to withdraw from study participation. An LAR s consent for the subject to participate is not sufficient if the subject refuses to participate, unless participation in the study holds out the only prospect for direct therapeutic benefit to the subject since all other potentially beneficial therapy has been exhausted. c. If the IRB approves a study where the enrollment of subjects whose decisional capacity may change, the plan for managing this should be included in the protocol summary. In general, the guiding principles should be 1) obtaining consent directly from the subject when possible, and 2) protecting the subject s right to withdraw d. The use of an LAR must be approved by the IRB prior to participant enrollment e. When LARs are involved, their role should be documented and, after the elements of consent have been reviewed, their consent should be recorded in the informed consent document in the same manner as if the subject were giving consent directly In addition, the informed consent may not contain any exculpatory language: Subjects may not be asked to waive (or appear to waive) any of their legal rights, nor may they be asked to release the investigator, sponsor, or institution (or its agents) from liability for negligence Participants Unable to Read A. If a participant is unable to read or if a legally acceptable representative is unable to read, an impartial witness should be present during the entire consent discussion 1. After the written consent document and any other written information to be provided to subjects, is read and explained to the subject or the subject s legally acceptable representative, and after the subject or the subject s legally acceptable representative has orally consented to the subject s participation in the trial and, if capable of doing so, has signed and personally dated the consent document, the witness should sign and personally date the consent document By signing the consent document, the witness attests that the information in the consent document and any other written information was accurately explained to, and apparently understood by, the subject or the subject s legally acceptable representative, and that consent was freely given by the subject or the subject s legally acceptable representative 2. If a short form is approved by the IRB (elements of consent have been presented orally), there must be a witness present to the oral presentation. The witness signs the short form and the written summary. Additionally, the short form must be signed by the person obtaining consent, by the subject, the subject's LAR, or the parent 13

14 Non English Speaking Participants The federal regulations require that informed consent information be presented in a language that is understandable to the subject. Discussions with subjects who are not fluent in English about their participation in the trial should be conducted with a translator. The translation services should be arranged ahead of time, if possible. Translator may be a member of the study team, but should not be a family member. Federal regulators and the SSH IRB strongly encourage the use of these procedures whenever possible. 1. If a study team plans on enrolling non-english speaking study participants, the entire consent document must be translated into a language understandable to the participants. The translated document must be approved by the IRB. This is typically done at the time of initial IRB review. The subject (or legally authorized representative), translator, and person obtaining informed consent must sign the translated version of the consent. 2. Investigators cannot always anticipate the interest of a particular non- English speaking individual and therefore may not be able to obtain an IRBapproved translated consent document in a timely manner. In such cases, the regulations do permit the use of a short form. The short from is written in a language understandable to the subject and outlines what he or she must be told by the investigator during their discussion about his or her participation in the trial. The short form must be accompanied by a written summary of what is presented orally (the IRB-approved English language consent document may serve as the written summary). The subject should be given copies of both. The translator must orally present the English language consent form. The subject (or legally authorized representative) and the witness* should sign the short form. The person obtaining consent and the witness* should sign the summary (or English language consent document). *An individual who is fluent in both English and the language understandable to the subject must witness the entire consent process. The translator may serve as the witness. The consent process must be appropriately documented in the subject s medical/research record. 14

15 Assent For research involving children, permission from the potential subject's parent or guardian must be obtained unless this requirement is waived by the IRB. When the IRB determines that assent is required; it shall also determine whether and how assent must be documented. Child assent is required, except when: 1. The IRB determines that the capability of some or all of the children is so limited that they cannot reasonably be consulted 2. The intervention or procedure involved in the research holds out a prospect of direct benefit that is important to the health or well-being of the children and is available only in the context of the research When a child who was enrolled in research with parental or guardian permission reaches the legal age of consent, the investigator should obtain informed consent from the subject unless the IRB approved a waiver of informed consent. 12. Indicate if you are requesting a waiver or alteration of consent/assent/parental permission and provide justification for the request. Waiver or Alteration of Consent A. The IRB may waive the requirement for the investigator to obtain a signed consent form for some or all subjects if it finds either: 1. That the only record linking the subject and the research would be the consent document and the principal risk would be potential harm resulting from a breach of confidentiality; or 2. That the research presents no more than minimal risk of harm to subjects and involves no procedures for which written consent is normally required outside of the research context B. The IRB may approve a consent procedure which does not include, or which alters, some or all of the elements of informed consent, or waive the requirements to obtain informed consent provided the IRB finds and documents that: 1. The research involves no more than minimal risk to the subjects; 2. The waiver or alteration will not adversely affect the rights and welfare of the subjects; 3. The research could not practicably be carried out without the waiver or alteration; and 4. Whenever appropriate, the subjects will be provided with additional pertinent information after participation 14. Data Analysis: Describe plans for data and statistical analysis, including stopping rules, endpoints, and provisions to monitor the data for the safety of participants. Describe plans to report problems and inform subjects of research results. 15. Institutional Support: Please identify departments not under the control of the 15

16 investigator that will be involved in this research (e.g., laboratory, pharmacy, nursing, health information management etc. Prior to initiation of study, each department must review protocol and agree to participate. 16. Multi-Site Research: Describe the management of information (e.g., unanticipated problems involving risks to participants or others, interim results and protocol modifications) among sites to protect participants. 17. FDA Regulated Research: List all drugs or devices under investigation. Indicate FDA status (investigational, new use of FDA approved drug or device, FDA approved drug or device within approved indications). Attach FDA required documents. FDA Form 1572 This form is a required component of all IND applications. It provides the name and address of the institution where the clinical investigation will be conducted, the names of the PI and all other sub-investigators, and other pertinent trial information. The FDA Form1572 outlines the duties and obligations of investigators. It is imperative that all investigators read it. The overall investigator within SSH is the only one required to sign the 1572, committing to all the rules and regulations set by the FDA for conducting clinical trials. Curriculum vitae (CV) are required for the PI and for all other investigators as evidence that they are qualified as an expert in the clinical use of the drug under investigation. The completed form is submitted to the sponsor, who then incorporates the information into an IND application. Clinicaltrials.gov Law requires that trials registered through ClinicalTrials.gov be managed and validated locally before they are published within the system. Registration should occur after IRB approval and before the first subject is enrolled. There is shared responsibility between the sponsor and lead investigator to register the trial. Investigators and study staff may refer to the chart below for guidance. RESEARCH TYPE Industry-initiated and-funded Federally funded (includes NIH, CTEP, and NCI Cooperative Groups) PROCEDURES Contact the pharmaceutical sponsor to determine the registration responsibility. Contact clinicaltrials.gov directly. Instructions on how to submit information are available at In-house, investigator-initiated Contact the Office of Research at (781) to speak with the registration coordinator at SSH to facilitate the registration process and resolve questions associated with trial information. 16

17 Writing a Research Protocol Sections of a protocol document will often include: Study Schema Summary of the Study Background and Significance Statistical Considerations Study Objectives and Endpoints Enrollment and Registration Information Eligibility Criteria Pre-Therapy Evaluations Treatment Plan Expected Adverse Events, Dose Modifications and Un-blinding Information Drug Information Reporting of Adverse Events Data Collection & Required Data Tables Follow Up Monitoring of Study Participants Long-Term Follow Up/Survival Data Collection Submission of Collected Research Specimens; Ancillary Studies Information Study Organization References Appendices A protocol must be implemented exactly as it is approved. Any changes to be made must be approved by the IRB prior to implementation, unless the safety of research subjects enrolled is at stake. Sponsor Protocol Submit this document if applicable Grant Application Submit this document if applicable Research Tools Submit all data collection instruments and educational materials to be used in the study. All documents should include a version date. Case report forms do not require IRB review, and these should not be submitted for review Advertisements All advertising materials must be reviewed and approved by the IRB prior to distribution. All documents should include a version date. Advertisements should not include any exculpatory language or be coercive. Advertisements may not allow compensation for participation in a trial offered by a sponsor to include a coupon good for a discount on the purchase price of the product once it has been approved for marketing. Advertisements may state that subjects will be paid but should not emphasize the payment by such means as larger or bold type. 17

18 Advertisements should include: Name and address of the clinical investigator and/or research facility Condition under trial and/or the purpose of the research The criteria that will be used to determine eligibility for the trial Brief list of participation benefits, if any (e.g., a no-cost health examination) Time or other commitment required of the subjects and Location of the research and the person or office to contact for further information Recruitment Letters/Phone Scripts/ s All documents should include a version date. The following should be included in recruitment materials: 1. A statement that a research trial is being conducted 2. An explanation of the purpose of the research 3. A brief description of what is involved in the research 4. The expected duration of participation 5. An opt-out or opt-in a) Opt-out: Either a telephone number to call or a postcard to return if the subject is not interested. If neither is returned, the investigator may then attempt one final contact to determine whether the subject is interested in learning more about participating in the trial. The optout must be justified due to the required effort of the potential subject. b) Opt-in: Either a telephone number to call or a postcard to return if the subject is interested in learning more about participating in the trial. In this case, the investigator may not contact subjects who have not called or returned the postcard. The return postcards should never contain information regarding a medical condition, medication, or diagnosis of those being contacted. Note: The SSH IRB does not allow investigators to recruit their employees, students, or anyone working under them to be volunteers in their research trial. Employees and students from other departments may be recruited to participate in such trials. Financial Disclosure by Clinical Investigators All investigators and study staff are required to adhere to the SSH Conflict of Interest policy and disclosure at the time of initial review or at the time of a new conflict. Investigators or staff with a financial conflict of interest must submit the financial conflict of interest form. Under this policy, investigators, their family members, and associated entities may not have a financial interest in a business that owns or licenses (including an option to license) the technology under study unless the financial interest does not exceed specific income or equity limits. 18

19 Income: The income limit is defined as $5,000 per 12-month period, including any compensation or gift from the Business, either directly or through an agent*. *Excluded from this restriction is the receipt of Income that results from the institution s supervised sponsored research or royalties under an institutional royaltysharing plan. Equity: This includes any ownership in the business, be it stock, stock options, or in any other form*. The limits are based on requirements for federally funded research: $5,000 or 5% ownership in the Business sponsoring research. *Excluded from this restriction is ownership of a mutual, pension, or other institutional investment fund over which the Participant does not exercise control. When the investigator, including Family Members or Associated Entities, own Equity in the Business, additional conditions must be met, no matter what the value of the ownership. The Equity must be: Publicly traded (sold on a stock market) or non-publicly traded entities Widely and closely held (owned in significant part by individuals who are not/have not been employed by the Business or Family Members, or by individuals who support the Business) Acquired independently of the research (for example, it was inherited from parent(s), or the Equity was purchased before the investigator had or contemplated a professional relationship with the Business) Travel Reimbursements and Sponsored Travel: This includes any reimbursed travel or sponsored travel related to institutional responsibilities. The Hospital will determine if any travel requires further investigation, including determination or disclosure of the monetary value. Continuing Review Submit the Continuing Review form along with study materials that will be used in the upcoming approval period. If the study is closed to enrollment, a consent form does not need to be submitted with continuing review. The continuing review form and all required documents should be submitted at least 30 days prior to the expiration date to allow adequate time for IRB review and to avoid any unnecessary delays. If a study requires full board review, the investigator must follow the IRB submission deadlines to ensure the continuing review is placed on an agenda prior to the expiration. If study approval expires, the Investigator will cease all research activities as instructed in the expiration notice. The Investigator immediately submits the application for continuation and/or notifies the IRB of study closure. Investigators are required to notify sponsors of any lapse in approval 19

20 Study Closure Studies may be closed when: all participants have completed all research-related interventions/interactions, collection of private identifiable information is completed, and analysis of private identifiable information is completed. Analysis can continue indefinitely when the data has been de-identified and the coding system, i.e., link, has been destroyed. Submit the form: Continuing Review Form Research Records At a minimum, Investigators must maintain research records for at least six (6) years from the date the research is closed with the SSH IRB. Beyond six years, requirements for record retention vary with the type of research conducted and provisions of the Investigator s funding source. It is the Investigator s responsibility to have a clear understanding of the retention requirements of a sponsor and to retain records for either the length of time required by the sponsor or for the length of time required by the SSH IRB, whichever is longer. All research records must be accessible for inspection and copying by authorized representatives of the IRB, Federal regulatory agency representatives, and the department or agency supporting the research. In the event the Investigator moves to another location and leaves SSH, the SSH IRB must be notified. The Investigator may either have another Investigator assume Principal Investigator responsibilities, close each of his or her research studies with the IRB, or take the research studies to the new location. The Investigator must also notify in writing to the SSH IRB the plan for either destroying the data or transferring the data to another PI. Modifications to Previously Approved Research All study changes require IRB review and approval prior to implementation. Attach tracked changes and clean copy versions of revised documents. Update the document version date. Submit the form: Amendment Submission Form Note: Proposed or anticipated changes to an exempt study must be submitted to the IRB for approval prior to initiation of changes if those changes may affect the exemption status. Exception An exception to the requirement for prospective IRB review of protocol changes when a protocol change is made to eliminate an immediate hazard to research subjects and/or to others. Submit the form: Problem Reporting Form Review and Approval of Other SSH Departments/Committees 20

21 The Office of Research assists in the coordination of review with ancillary departments involved in the research activity. Investigators will be informed of other review requirements needed for approval. No project may be activated until all relevant ancillary departments have granted approval. Review Outcomes Approve: The protocol and accompanying documents are approved as submitted. Final approval will commence on the day the trial is approved by an action of the convened IRB or chairperson or designee and expire within one year of the meeting date but not later than the day preceding the date of review. Subjects may not be recruited into the trial until final approval has been issued and administrative requirements are satisfied. Approval Requiring Modifications: Modifications are required. Minor or prescriptive changes or requirements may be reviewed for approval by the IRB chair or designee. Any uncertainty or question about the investigator's response will be referred to the full committee for additional review. Investigators are asked to respond to questions or requested revisions to a trial or trial material within 60 days of the review. Failure to respond within 60 days may require that the PI submit a new application. Defer: Protocols are deferred when significant questions are raised during the review. The investigator will be informed in writing of the required changes and requested information and must provide the IRB with a response within 60 days from the date of the review. The IRB will consider the submission withdrawn if the investigator fails to respond within 60. Table: The IRB may table a review due to inadequate time or members present to conduct a thorough review. In this case, the investigator will be notified and the review will be rescheduled for another meeting. Disapprove: A protocol may be disapproved where it fails to meet one or more of the criteria used by the IRB for approval of research. The investigator will be given a detailed memo describing the issues related to this disapproval. The investigator is allowed to respond to the IRB in person or in writing regarding this decision. Disapproval cannot be given through the expedited review mechanism and may only be given by majority vote at a convened meeting of the IRB. If the IRB disapproves a trial, no other review body or person may grant approval. 21

22 PROBLEM REPORTING The following items should be reported to the IRB within 5 working days: Information that indicates a change to the risks or potential benefits of the research. For example: o Change in FDA labeling or withdrawal from marketing of a drug, device, or biologic used in a protocol o An interim analysis, safety monitoring report (including DSMB reports), publication in the literature, or revised investigator brochure that indicates an increase in the frequency or magnitude of harm, uncovers a new risk, or provides more information about the benefits of the research. *DSMB reports that do not indicate a change in risk/benefit should be submitted at continuing review Adverse event that, in the opinion of the investigator, is unexpected and at least possibly related to the research procedures (report death, life threatening events, and hospitalizations only if these are outcomes of the adverse event) o A harm is unexpected when its specificity and severity are not accurately reflected in the protocol summary, detailed protocol, and/or consent document o A harm is possibly-related when there is a reasonable possibility that the incident, experience, or outcome may have been caused by the research procedures Unanticipated problems involving risks to subjects or others that is (1) unanticipated; (2) related or possibly related to participation in the research; AND (3) indicates that the research places participants or others are at increased risk of harm than was previously known or recognized External adverse event that, in the opinion of the sponsor or investigator, requires changes to the protocol and/or consent document. Regulatory non-compliance or allegation of regulatory non-compliance (e.g. conducting human research without IRB approval) Audit, inspection, or inquiry by federal agency Failure to follow the protocol due to the action or inaction of the investigator or study staff Breach of confidentiality Change to the protocol to eliminate an apparent immediate hazard to a participant Incarceration of a participant in a protocol not approved to enroll prisoners Complaint of a participant that cannot be resolved by the study team Submit the form: Problem Reporting Form IND/IDE Safety Reporting IND safety reports are AE reports submitted by sponsors to local investigators detailing any AE that occurs at other sites. These reports must be submitted to the Office of Research upon receipt. A cover memo may be necessary to identify the study. 22

23 IND safety reports reflect the evaluation of the event by the investigator at whose site the AE occurred. If the SSH investigator does not agree with the evaluation of the event, the SSH investigator note his or her assessment of the event. Submit the form: Problem Report Reminders When Submitting Problem Reports Handwritten reports are not accepted. All reports must be typed. Do not send any PHI to the Office of Research PRIVACY AND CONFIDENTIALITY Health Insurance Portability and Accountability Act (HIPAA) Under HIPAA, trial subjects are required to authorize the use and disclosure of their protected health information (PHI). According to the Rule, trial subjects have the right to: 1. Access their PHI; 2. Request amendment of their PHI; 3. Receive an accounting of disclosures of their PHI; 4. Request restrictions on the uses and disclosures of their PHI; 5. Request receipt of communications of their PHI by alternative means or at alternative locations; and 6. Revoke their authorization for use and disclosure of their PHI. Access: Research subjects are entitled to access (i.e., inspect and copy) their PHI that is maintained in a designated record set. The Rule defines a designated record set as the provider s health care and billing records about individuals and any records used by the provider to make health care decisions about individuals. Therefore, the designated record set includes PHI that is generated in research and recorded in the medical record or in billing records as well as PHI that is recorded elsewhere, such as the trial files, but is also used to make health care or billing decisions. It is important to note that information that is generated in research and lacks clinical validity or clinical utility generally will be considered outside the designated record set (unless it is recorded in the medical or billing records), and thus the Rule s right of access generally does not apply to such information. The Rule permits researchers conducting clinical trials to suspend subjects rights of access temporarily, for as long as the research is in progress, if the subject specifically agrees to this suspension in the research authorization. The right of access must be reinstated when the research is complete. Amend: Research subjects are entitled to request that the researcher amend their PHI that is maintained in a designated record set. Subjects may only amend PHI to which they have a right of access under the Rule. If the subject s request to amend is granted, the researcher must inform the subject, the people or entities the subject identifies as needing the amendment and others who may rely on the information of the amendment. 23

24 Restrict: Research subjects are entitled to request that the researcher restrict the uses and disclosures of their PHI. However, the researcher is not required to agree to the restriction. If the researcher does not agree, the subject can decide whether he or she still wants to participate in the research. If the researcher does agree, the restrictions must be followed except if necessary to provide emergency treatment to the subject. Researchers must also communicate any restrictions to which they have agreed to other individuals or entities to which they permissibly disclose the subject s PHI. Alternate means or locations: Research subjects are entitled to request receipt of communications of PHI from the researcher by alternative means or alternative locations (at a home address versus a work address). The researcher must accommodate such requests if reasonable but may require the subject to specify an alternate address or other method of contact. The researcher may not require the subject to explain the basis of the request. Revoke: Research subjects have the right to revoke their authorization for the researcher to use and discloses PHI in connection with the research, except to the extent that the researcher has already relied on the authorization. As a result, if the PHI has already been used to perform an analysis or other evaluation for the trial, the results of that analysis can be retained but the researcher must notify the IRB regarding the subject s revocation. The researcher may also continue to use the subject s PHI as necessary to account for the subject s withdrawal from the trial or to report adverse events. However, the researcher generally may not use or disclose the PHI in new ways after the revocation. Researchers must inform other individuals or sites involved in the research of any revocation of authorization. What Constitutes PHI? The following are all considered PHI: Names Addresses Dates that directly relate to the individual including birth date, death date, discharge dates Telephone numbers Fax numbers addresses Social security numbers Medical record and pathology record numbers Health plan beneficiary numbers Account numbers Certificate/license numbers VINs, serial numbers, and license plate numbers Device identifiers and serial numbers URLs IP addresses Biometric identifiers including finger and voice prints Full-face photographic images and comparable images 24