Research at Aadil Hospital must be carried out in an ethical manner. The basic ethical principles guiding research involving human subjects are:
(Reference :The Belmont Report)
The institution established an independent IRB and empowered it to protect the rights and welfare of human research participants. The purpose of the IRB is to review and approve, require modifications in (to secure approval), or disapprove all human research activities in order to assure that the rights and welfare of individuals involved as subjects of research are being protected in accordance with applicable regulations.
The Chairperson is responsible for ensuring that the IRB functions independently, and that members have direct access to him/her if they experience undue influence or if they have concerns about the IRB. The Chairperson/Vice Chairperson cannot approve a study that has been disapproved by the IRB. IRB fosters institutional culture that supports the ethical conduct of all research. IRB members (including the Chair) should remove themselves from the review of any research in which they or close family members have a conflicting interest.
The Chairperson gives the IRB full authority:
Research Investigators and Study Staff
The Principal Investigator (PI) certifies that he/she will conduct the study according to applicable laws, regulation, ethical standards and guidelines governing the protection of human research subjects. The Principal Investigator is required to be qualified by training, and assumes ultimate responsibility and oversight for the protocol to conduct research according to sound research design, assures adequate resources are available, selects and oversees trained study staff and delegates duties prospectively and consistent with Scopes of Practice to research team members, assures that human research training requirements are met, weighs risk benefits for subjects, implements fair recruitment, responds to subject complaints or requests for information, develops an informed consent process, minimizes risk and develops plans to monitor safety and detect harm, reports safety findings and unanticipated problems, discloses conflicts of interest, adheres to IRB Conditions of Approval, national regulations, sponsor and organizational policy in order to conduct the study appropriate to human subject protections. Investigators are required to submit complete protocols and relevant study related materials to the IRB for review, including continuing reviews and status updates as required by the IRB.
Promptly Reporting Changes in Principal Investigator (PI) :this means promptly reporting any changes in the PI to the IRB. Changes in the PI must be reviewed and approved by the IRB prior to the initiation of the change to ensure the new individual meets the criteria for conditions of approval.
The IRB is subject to regulation and inspection by governmental regulatory agencies (e.g. DRAP) and sponsor representatives/CROs.
The IRB has five voting members. Members and alternates are appointed in writing by IRB Chair and members for 3 years and may be re-appointed for 3 year terms. Committee composition is reviewed annually according to the following criteria: (1) professional representation, (2) diversity, (3) institutional knowledge, (4) gender representation, (5) voting status, (6) training and background, (7) potential conflicts of interest, (8) if one member’s primary concerns are in scientific areas, (9) if one member’s primary concerns are in non-scientific areas, (10) if community members are not associated with Aadil hospital or are not part of the immediate family of a person who is affiliated with Aadil, (11) if IRB membership is appropriate given the research being reviewed, (12) if membership includes representatives with an interest in or experience with vulnerable populations either as members or ad hoc consultants, (13) if alternate members have appropriate training and backgrounds to serve as replacements, (14) if ad hoc reviewers are utilized when IRB members do not have the expertise necessary to adequately review research, and if (15) the number of IRB meetings and the frequency of meetings are adequate for the number and types of studies.
The Chairperson has expert knowledge in human subject protections. The Chairperson must be a highly regarded and respected leader in order to promote respect for the IRB’s advice and counsel throughout Aadil Hospital and externally.
The Chairperson is appointed in 3-year increments and may be reappointed for 3 year terms indefinitely.
The Chairperson has primary responsibility for conducting Committee business. He/she directs Committee proceedings in accordance with institutional and regulatory requirements. He mentors Committee members, institutional officials, and investigators to ensure that the rights and welfare of research subjects are protected. He/she functions as a role model and conducts business fairly and impartially. He/she is the signatory official for official IRB minutes and official IRB correspondence. He/she may delegate signing authority to Committee members
If necessary, the Director Aadil Hospital may relieve a Chair or Vice-Chair from the Committee service due to repeated non-attendance, lack of participation in continuing education, or other problematic performance issues. Should this action be required, the Director will notify the Committee members.
Length of Term/Service
Members serve terms in three-year increments and may be re-appointed. Due to the long learning curve and extensive training requirements the institution strives to keep IRB member turnover at a minimum.
Duties
Committee members are responsible for assuring that the rights and welfare of research subjects are protected, that risks are minimized and that benefits outweigh risks. Members vote to approve, require modifications (in order to secure approval) or disapprove submissions. These actions include: (a) initial reviews, (b) continuing reviews, (c) amendments, (d) serious adverse events, (e) sponsor serious adverse events (f) unanticipated protocol deviations, (g) advertisements, (h) consent form revisions (i) investigator brochure updates (j) protocol deviations, (k) minutes of previous meetings (l) investigator changes, (m) general policy issues and (n) non-compliance. The Committee has the authority to suspend or terminate an investigator’s research privileges if it is determined he/she is non-compliant.
Attendance Requirements and Training
Members are required to attend meetings. All seven members have alternates. An alternate member may only substitute for his/her designated member. The IRB ensures that initial and continuing education requirements for the IRB Chair, IRB members, and IRB alternate members are met.
Annual Performance Evaluation
The IRB Chairperson considers the following criteria when evaluating IRB members: (a) thoroughness in reading of IRB meeting material; (b) level of participation in discussion; (c) meeting attendance; (d) does member provide appropriate representation for his/her professional background; (e) knowledge of human research protection regulations and guidelines; (f) dedication and sincerity to patient advocacy role.
Removal
The Chairperson is responsible for suspending or terminating membership of any individuals who are not fulfilling their member responsibilities or obligations.
The IRB meets fortnightly on Tuesday (with exceptions for holidays, weather, etc.) and meetings last approximately three hours.
The organization employs one full time IRB Administrator/Secretary devoted exclusively to support IRB activities.
The IRB Administrator maintains information files for all IRB members. These files are stored in paper form in the IRB office and are electronically maintained as well.
The IRB agenda is prepared for each IRB meeting as submitted items are added to the agenda. Common agenda categories include the following:
Agendas and Minutes are filed in the IRB office.
Minutes are required to document relevant discussion of the above reviewed items and to document the actions of the IRB. Minutes are required to include, separate deliberations for each action; votes for each protocol as numbers for, against, or abstaining; the names of IRB members who left the meeting (recusal) because of a conflicting interest along with the fact that a conflicting interest is the reason for the absence; attendance of members or alternate members including those who participated through videoconferences or teleconference, and documentation that those members received all pertinent material before the meeting and were able to actively and equally participate in all discussions.
The IRB requires that a complete set of all materials relevant to review of the research and correspondence to researchers regarding IRB actions be maintained in study files. The IRB records include for each protocol’s initial and continuing review, the frequency for the next continuing review (as applicable). The IRB and investigators will keep study records in accordance with hospital policy, and as required by the protocol, GCP and regulatory guidelines. CV’s and training records for study staff are maintained in research centre and furnished to IRB as and when required. CV’s and training records for IRB members are maintained in the IRB Administrator’s/Secretary office in a secure filing cabinet until they are indexed and archived at the approved long-term storage facility designated by the research office. All records must be maintained in a secure environment.
The original IRB Approved Consent Form is stamped and provided to the investigator and a copy is filed. The IRB requires that the stamped version of the consent form be used to consent subjects. If the investigator leaves the hospital facility the original research records must be retained at the institution and archived.
All IRB records are kept in secured locked areas and may be accessed by authorized individuals and entities on a need to know basis. Access to IRB records is limited to the IRB Chairperson and members, IRB Administrator and office staff, authorized representatives and officials of the regulatory agencies-DRAP, including the sponsor monitors.
Should researchers or their study staff need to review IRB files, the IRB staff will pull what is requested and provide a copy to the requestor. In the unlikely situation that an investigator and/or their research staff request permission to review their IRB record folders this may be done ONLY in the full-time presence of an IRB staff person.
All other access to IRB records is limited to those who have legitimate need for them as determined by the Director or Chairperson.
The IRB and investigators will keep a complete set of all research study records. The IRB and investigators will keep study records in accordance with hospital policy and as required by the protocol and regulatory law.
Research records are stored in secure research locations within the research center. A “Certificate of Destruction” will be issued by the record storage facility and filed in the IRB office. All Research records must be made accessible for review and copying by authorized officials of oversight regulatory body (DRAP).
Education and training records are kept in the IRB and Research Centre Office.
Formal communications from the IRB are written and all determinations are conveyed in writing. Copies are filed in the IRB’s investigator project file and are maintained in an electronic form too.
If there is any element of research in any activity involving human subjects, the activity (including screening procedures and subject recruitment) must undergo IRB review before it can start. No study can be initiated until approved by the convened IRB or expedited reviewer (when appropriate).
The IRB meets every two weeks in the IRB Conference room. Scheduled meetings will be canceled or re-scheduled for federal holidays, lack of a quorum or for cause at the direction of the Chairperson
The IRB requires that all members receive all submission materials including minutes of the previous meeting in time to conduct a thorough review at convened meetings of all agenda items in order to determine if the research meets regulatory criteria for approval and for review of modifications to previously approved research in order to determine whether modified research (i.e. amendments) continue to fulfill the regulatory criteria for approval. One copy of the protocol, investigational brochure, approved consent form and any newly proposed consent form, amendment, advertisement, serious adverse event, continuing review, completed investigator submission forms or other material to be reviewed must be received in the IRB Office by a week before in order to be reviewed the following week. IRB staff prepare a written agenda, make copies of materials submitted by the investigator, and make copies of the previous week’s IRB minutes for distribution to IRB members The schedule may be adjusted for holidays, weather or other unanticipated circumstance. Members are given a minimum of four days to review materials.
The IRB reviews all submitted items at a convened meeting. Reviews and determinations are documented in Committee minutes. Written notifications of review, approval, disapproval or actions required are sent to the investigator. Reviewed items along with a file copy of the written notification are filed in the protocol folder and kept in the IRB office.
The IRB reviews and has the authority to approve, require modifications in (to secure approval) or disapprove all human research activities conducted at Aadil Hospital. In order to secure IRB approval, the IRB must receive adequate information from the investigator and sponsor to determine:
The IRB is required to conduct continuing review of human subjects research at intervals appropriate to the degree of risk, but not less than once per year, except in the following cases:
Continuing review approval of research must occur on or before the date when approval expires. When continuing review is not completed prior to the expiration of the current approval period, there is an automatic lapse of IRB approval. All research must stop unless the IRB Chair determines that it is in the best interest of individual participants to continue the research interventions or interactions.
For research requiring continuing review, ccontinuing Review is allowed to stop only when (1) the research is permanently closed to the enrollment of new participants, (2) All participants have completed all research-related interventions, and (3) collection and analysis of private identifiable information has been completed.
The Subject Lists are submitted by the Investigator and by the Investigational Pharmacist and are secured in the IRB Office. The information is cross-referenced by the IRB office staff prior to the meeting. Discrepancies are reported to the IRB during the review of the projects. The Subject Lists are filed with the Continuing Review event.
If a PI has not provided continuing review application materials to the IRB, or the IRB has not approved the continuing review application by the IRB approval expiration date, the IRB approval automatically lapses and all research activities must stop, including data analysis of personal identifiable information. No enrollment of participants can occur.
If the continuing review application is not approved by the IRB approval expiration date, all research activities must stop.
The IRB will notify the PI, the sponsor funding the project, affected participating sites, of lapses of study approval. Correspondence will be prepared by the IRB administrative staff to be reviewed and signed by the IRB Chair. Correspondence will be sent by encrypted email with a read receipt requested.
If the lapse occurred due to non-submission of the continuing review applications by the PI, the PI may submit the request for continuing review application, along with a justification for the delay in submission, up to 30 days after the expiration of approval date in order for the review to still be conducted by the IRB. After the 30 days have elapsed, the project or site will be considered noncompliant and the Board will proceed in accordance with reporting per the requirements outlined for reporting Serious and Continuing Noncompliance in this policy and consider the study or site for termination. If study or site termination is not in the best interest of participants, the study may be continued until the participants have safely completed the study or can be withdrawn but no new enrollment can take place.
If the PI wants to re-open a study that lapsed and it has been over 30 days since the lapse occurred, a new PI study application must be submitted, or the PI can consult with the IRB Administrative office regarding any documentation that may be required, in addition to the continuing review application, for the review to take place.
If the PI submitted all the required documents by the expiration date, but the approval period lapses, all the actions outlined above must still take place. The IRB will review the submitted materials as soon as practicable.
(Requirement - all IRB members receive personal copies of all study materials to be reviewed at convened IRB meetings)
Items submitted for review include but are not limited to:
The Principal Investigator is required to submit the Modification to Approved Research to IRB including a justification for the amendment (signed), a complete description of the proposed changes,
a summary of changes, and amended protocol as appropriate. Items submitted for review include but are but are not limited to:
If the proposed amendment or modification involves the informed consent or conveying new information, the PI must indicate whether participants who have already consented to participate need to be re-consented and/or informed.
Five IRB voting members must be present to achieve a quorum. Quorums can be lost if a member or members have to leave a meeting early or absent themselves due to conflicts of interest. In such circumstances affected projects would be deferred until a quorum was re-established or postponed until the next meeting. The IRB Administrator/Secretary is responsible for monitoring and ensuring the required quorum is maintained during IRB meetings, including special IRB membership requirements if research involves pregnant women, minors/children.
Each voting member has one vote.
Voting members who have conflicts of interests are required to recuse themselves from deliberations leave the room, and not vote. Conflicts of interest include circumstances where financial, professional, or other personal issues are involved.
(Note: A printed copy of IRB Conditions of Approval is mailed to investigators with each Initial and Continuing Review Approval Letter)
Provide a copy to the subject or LAR signing the form and keep the original for your files.
This policy applies to all human subjects research conducted at Aadil hospital, as well as investigators, IRB members and staff, and institutional officials. Others who may report possible unanticipated problems include participants, participant’s family members, sponsors and other auditors.
Members of the research centre/project are required to report and the IRB is required to review reports of unanticipated problems involving risks to subjects or others (e.g. adverse events, complaints from participants or others, protocol deviations, new safety information, DSMB/data monitoring committee reports as well as any other event that influences the risk benefit analysis of the research. The IRB determines whether these reports were unanticipated problems involving risks to participants or others and takes required actions including notifications of subjects, suspension, termination and reporting to relevant institutional officials/entities (e.g. DRAP)
Definitions
Adverse Event (AE) - is any untoward physical or psychological occurrence in a human subject participating in research.
Related AE, Death or Problem – is an AE, death or problem that may reasonably be regarded as caused by or probably caused by the research.
Serious Adverse Event (SAE) - is an untoward occurrence in human research that results in death, a life-threatening experience, inpatient hospitalization, prolongation of hospitalization, persistent or significant disability or incapacity, congenital anomaly, or birth defect., or that requires medical, surgical, behavioral, social, or other intervention to prevent such an outcome.
Unanticipated and Unexpected Problems – The terms refer to an event or problem in research that is new or greater than previously known in terms of nature, severity, or frequency, given the procedures described in protocol-related documents and the characteristics of the study population.
Examples of materials provided to and reviewed by IRB: - Unanticipated Problems. As warranted, the IRB may review relevant reports such as, protocol, investigational brochure, consent documents, IRB Continuing Reviews and protocol material deemed relevant. The IRB assesses reports of potential sources of unanticipated problems such as:
Within 5 business days after receiving written notification of an SAE or serious problem, the IRB Chair or a qualified IRB member-reviewer must determine and document whether any actions are warranted to eliminate apparent immediate hazards to subjects.
Examples of actions the IRB may take as appropriate:
Definition
(In order to approve research, the IRB ensures that the consent process meets the criteria for approval)
IRB determinations will be communicated in writing to the investigator. Official IRB correspondence is maintained in computerized form and hard copy file.
The IRB may request additional information from the Principal Investigator or sponsor to enable appropriate review. Investigator responses should be received within 30-60 days unless an earlier response is required due to a subject safety issue.
IRB determinations are conveyed to the Principal Investigator in writing within one week of the IRB meeting and include actions required if applicable.
The IRB normally does not notify sponsors of IRB determinations. The Principal Investigator serves as the communications link between the IRB and the sponsor. There may be circumstances where the IRB feels it is necessary to directly notify the sponsor (e.g. suspension, termination).
Investigators may appeal IRB decisions. Appeals should be accompanied by a cover letter that explains the basis of the appeal. Principal Investigators, study coordinators and/or sponsor representatives may attend, or be requested to attend an IRB meeting. Investigators and coordinators are encouraged to contact IRB staff and IRB members to discuss concerns without compromising the integrity of the process.
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Investigators are responsible for oversight and management of all aspects of the research as outlined in the IRB approved protocol and as conducted by the research staff. Investigators must effectively communicate with the IRB and respond to requests from the IRB in a timely manner. S/he must be available to the IRB during meetings and/or reviews.
The IRB requires the submission of curriculum vitae for all study staff and requires that mandatory training be completed. Additional research training may be required prior to conducting research activities. If the IRB determines that the Principal Investigator and/or key research staff do not have the professional qualifications or resources necessary to conduct research in accordance with regulations this can be the basis for disapproval or a stipulation to involve individuals with appropriate expertise in the study. The IRB may consider investigator collaborations with other professionals who have the required expertise and who agree to serve as sub-investigators, preceptors, mentors, or medical monitors.
It is the investigator’s responsibility to maintain research records. This means maintaining written documentation on file that the protocol is being implemented as approved by the IRB and in accordance with other required approvals.
The IRB addresses many complex, overlapping and intermingled issues dealing with the basic question, “is there any possible benefit from this study and does the potential gain outweigh the potential risk?” In order to judge if criteria are met the Committee needs detailed information. If a protocol is submitted for review and Committee members believe that there is insufficient information to enable an appropriate review, a written request for additional information will be sent to the Principal Investigator. The investigator is responsible for the research protocol and for ensuring research compliance.
Initial and Continuing Review require investigators to provide detailed information about their proposed research
In order to approve research, the IRB must determine that selection of subjects is equitable. The IRB requires investigators to submit for review the final copy of all advertisements and recruitment incentives associated with the research that they oversee.
IRB recruitment procedures are designed to assure that informed consent is given freely and to avoid coercion or undue influence. To evaluate this the IRB needs to obtain appropriate information in order to know from what population the subjects will be drawn, what incentives are being offered, and the conditions under which the offer will be made.
To approve research, the IRB must determine that the selection of subjects is equitable. In making this determination, the IRB should evaluate the purposes of the research, the research setting, and the inclusion/exclusion criteria.
The purposes of the research are evaluated by the IRB during Initial Review. The IRB documents if the purpose is appropriate and if it should yield useful information.
Investigators are required to specify the study site in their Initial Review submission. The role of participating institutions, IRBs, and off-site research personnel including how they communicate with each other must be provided to the IRB for review. The IRB evaluates if adequate plans are in place to minimize potential risks due to lack of communication or misunderstanding of responsibilities between research sites. As part of its review the IRB evaluates the standard informed consent process to determine if modifications are required in order to minimize risks. The IRB may require as appropriate a formal inter-institutional agreement. Details of the IRB review and approval for off-site research are documented in IRB minutes and investigator correspondence.
Includes consideration that risks, burdens and benefits of research are distributed fairly. Includes consideration of:
Includes evaluation of the following:
The Investigational Brochure and/or package inserts will be reproduced and provided to members prior to the convened meeting when the relevant protocol is to be reviewed.
The case report form that is provided by the sponsor will be reviewed by the IRB