Policy:
The Research department of CANM is leased to Cardiology Associates Research, LLC, (CARe).  CANM and CARe will make every effort to ensure protocol compliance as well as compliance with state and federal regulations in the conduct of clinical research projects.

Procedures:

Research Project Initiation: The Clinical Research Manager will review each study protocol and prepare the budget for each new study. The protocol and budget will be reviewed by the Research Committee for approval. The Clinical Research Manager serves as a liaison with clinical research project sponsors during the site selection process. Once selected as a site, the Coordinator and/or Regulatory Specialist prepares required regulatory documents for submission and approval to the sponsor, contract research organization, and the local or central Institutional Review Board (IRB). Documents include, but are not limited to, informed consents, 1572s, copies of project protocols, investigator brochures, protocol summary, patient education plan, laboratory normal ranges and certification, signature pages, financial disclosure, curriculum vitae and licensure. The Clinical Research Manager will review and negotiate the study research agreement and budget between CARe and the study sponsor. The final agreement will be signed by a CARe Executive Officer, CARe Medical Director, and/or Principal Investigator. The assigned Clinical Research Manager will coordinate the negotiations between the North Mississippi Health Services (NMHS), attorney and sponsor to development of aLetter of Indemnification/Facility Use Agreement between the sponsor and NMHS if required. The Clinical Research Manager will arrange the site initiation visit from the sponsor with the Principal Investigator.

Data Collection and Protocol Compliance: The Principal Investigator is responsible for oversight of data collection and protocol compliance for research projects managed by CARe with assistance of the Research Coordinator(s). This includes, but is not limited to, eligibility screening, obtaining informed consent, clinical measurements, completion of case report forms, and submission of data to the project research center, maintenance of study documents and records, and maintenance of study drug/device and accountability.
The Coordinator will arrange all monitor visits from the sponsor with the Principal Investigator.

Clinical Research Project Procedures: The Principal Investigator and the Coordinator will perform clinical research procedures as per the research study protocol and as assigned by the Principal Investigator with competency. Competency will be demonstrated by maintaining skills through continual education and following: the Code of Federal Regulations Title 21, ICH Guidelines for Good Clinical Practice, Policies and Procedures for the NMHS and/or Central IRB, IATA Dangerous Goods Regulations, and HIPAA regulations.

Informed Consent: (Note: This information is an excerpt from North Mississippi Health Services IRB policies.)  Informed consent is more than just a signature on a form.  It is a process of information exchange that may include, in addition to reading and signing the informed consent document, subject recruitment materials, verbal instructions, question/answer sessions and measures of subject understanding.  The clinical investigator is responsible for ensuring that informed consent is obtained from each research subject before that subject participates in the research study. The investigator shall give the subject adequate opportunity to read it before it is signed.

Subjects will print, sign, date and time the consent form in their own handwriting and in the presence of the study coordinator or physician obtaining informed consent.  Should a subject bring a consent form to a baseline/screening visit already signed, that form will not be accepted; a new consent form will be signed and executed by the subject and study coordinator or physician at the time of the visit.

A subject who can understand and comprehend spoken English, but is physically unable to talk or write, can be entered into the study if they are competent and able to indicate approval or disapproval by other means.  The subject may be entered into the study if the subject retains the ability to understand the concepts of the study and evaluate the risk and benefit of being in the study when explained verbally, and the subject is able to indicate approval or disapproval to study entry.  The consent form should document the method used for communication with the prospective subject and the specific means by which the prospective subject communicated agreement to participate in the study. 

The FDA does not require the investigator to personally conduct the consent interview.  The investigator remains ultimately responsible, even when delegating the task of obtaining informed consent to another individual knowledgeable about the research. 

Informed consent shall be documented by the use of a written consent form approved by the North Mississippi Health Service IRB or Central IRB and signed by the subject. The Investigator will sign informed consent preferably at the time of subject signing, but no less than 24 hours after.  A copy shall be given to the person signing the form.  No informed consent may include any exculpatory language through which the subject or the representative is made to waive or appear to waive any of the subject’s legal rights, or releases or appears to release the investigator, the sponsor, the institution or its agents from liability for negligence.   

If the already approved informed consent document requires revision, the nature of the revision will determine the level of IRB review and the forum for informing the subject.  If the revisions to the informed consent form are minor, such as a change in phone number or address, or another change that will not affect the subject’s safety, such as a study schedule change, then the changes can undergo expedited review.  Subjects already consented may be informed via a letter.  If the revisions involve additional testing that will increase the subject’s risks or new information that may change the subject’s willingness to participate in the study, then the changes may require full review.  The already-consented subjects should be informed and asked to give their consent again.  This may be done by highlighting the differences on the new consent form. 

The informed consent process will be documented in the patient’s medical record.

Withdrawal of Informed Consent: Participation in a clinical trial is voluntary and as such, subjects can withdraw their consent to participate at any time and for any reason without affecting their ongoing medical care.  Efforts will be made, in accordance with the specific study protocol, to continue follow-up for study data.  Options for continued follow-up may include phone calls, office visits, or medical record review.  Details of a subject’s withdrawal of consent along with options for follow-up will be documented in the subject’s medical record.  In the event a subject completely withdraws from a study and declines options for continued follow-up, no additional contact for study purposes will be made. 

Multiple attempts to reach a subject via telephone call followed by certified mail and/or Federal Express with no response is an indication that the subject does not wish to be contacted further, therefore efforts to contact the subject should be terminated. 

Transporting Drugs:  All investigational study medications that are shipped to North Mississippi Medical Center are logged in at, and maintained at the North Mississippi Medical Center main unit pharmacy located at 830 South Gloster Street, Tupelo, Mississippi.  The pharmacy has designated pharmacists filling the roles of primary research pharmacist and secondary research pharmacist.  Once study drug is dispensed from the NMMC pharmacy, it is checked by the pharmacist and study coordinator, placed in a hand-held Igloo container and transported by private vehicle approximately 1.1 miles to the Cardiology Associates of North Mississippi clinic located at 499 Gloster Creek Village, where it is dispensed to the patient.

Storage of Investigational Drugs and Products:  For investigational drugs shipped to and dispensed from North Mississippi Medical Center Pharmacy, please reference NMMC Main Unit Hospital Pharmacy Storage Protocol.  North MS Medical Center Pharmacy is located at 830 South Gloster Street, Tupelo, MS  38801.

Investigational Products (such as coronary stents, implantable cardiac devices, leads, etc.) that are shipped to Cardiology Associates Research, LLC are received, acknowledged with the sponsor, logged into the device accountability logs, and stored in locked cabinets.  The locked cabinets are located within the CARe offices at 830 South Gloster Street, Third Floor East Tower, Tupelo, MS 38801 and with limited access to the cabinets.  The locked cabinets are housed in the CARe Workroom which also locks and has limited key-entry access.  Access to the CARe Workroom is limited to Research staff members only. 

Investigational drugs that are shipped to, stored, and dispensed from Cardiology Associates of North MS outpatient clinic located at 499 Gloster Creek Village, Tupelo, MS  38801 are received, acknowledged with the sponsor, logged into the drug accountability logs, and stored in locked cabinets in the Research Investigational Drug Closet.  The Research Investigational Drug Closet is located on Pod D of the clinic facility with key-entry access only granted to the Study Nurses listed on the delegation of authority logs; those nurses who are able to dispense study medications according to the specific study protocols as well as those who are licensed by the state of MS. 

Storage and dispensing of Schedule IV Medications:  Investigational Schedule IV drugs that are shipped to and dispensed from Cardiology Associates of North Mississippi outpatient clinic will be received, dispensed, maintained, and accounted for as per the Rules and Regulations of the MS Board of Medical Licensure, Title 30, Part 2640, Miss. Code Ann. §73-43-11 (Please refer to the attached Regulations).

The Research Investigational Drug Closet is equipped with state-of-the-art security locks, Medeco MVP cam locks.  Medeco MVP cam locks are manufactured from high density zinc die cast, and offer patented key control to prevent the unauthorized duplication of keys and maintain system integrity.  Medeco MVP cam locks design features a unique elevate and rotate pin tumbler design, double-locking action, making the locks virtually pick proof.  All Medeco keys and locks are protected under patent, trademark, and copyright laws.  Medeco keys may only be duplicated by Medeco or by a Medeco authorized sales outlet, and only at the request of the original purchaser of the lock.  The door of the Research Investigational Drug Closet is also equipped with an automatic closure arm, preventing the door from standing open.  The Medeco lock on the door handle is a one-way lock – the only way to open the door is with a key and once the door closes, it is locked.  Once inside, the door can be opened without a key from the inside; however, entrance from outside the closet is only with the Medeco key.

The temperature of the Research Investigational Drug Closet is maintained between 62 (F) and 76 (F) degrees with temperature recordings documented during business hours.

Investigational Drug Destruction:  Upon written notification of study termination, the study coordinator will complete any and all documentation regarding inventory of investigational product (IP) issued to the site.  Inventory documentation will include drug accountability of unused IP as well as IP dispensed to and returned by participating subjects.  Documents to be completed include the Study Drug Accountability Log and the CANM Record of Destruction of Investigational Product.

As mandated by federal law, all records involved must be kept for a period of two (2) years following the date a marketing application is approved for the drug for the indication for which it is being investigated.  If no application is to be filed or if the application is not approved for such indication, until two (2) years after the investigation is discontinued and FDA is notified.  In cases of international study centers, records must be kept for 15 years.

Procedure for Destruction:

1.  If IP container is sharp (needles, spikes, adapter devices, glass) it will be disposed of in the red, rigid biohazard sharps containers.

2.  If the material (IP) is considered a non-hazardous pharmaceutical, a biological drug, all IP contained therein will be disposed of in the red, rigid biohazard sharps containers.  If an IP container is considered empty or contains less that 3% of the original volume remaining, the IP and containers will be disposed of in the red rigid biohazard sharps containers.  The study coordinator will record the following information for all destroyed IP on the appropriate drug accountability log: drug name, kit/lot number, quantity destroyed, and date of destruction.

3.  Gowns, gloves, paper towels, and related waste generated in the destruction of IP will be disposed of in regular trash, unless gross contamination with hazardous substances is present.

4.  Disposition of IP generated waste is as follows:

a. Regular trash is collected by housekeeping staff and is transported from site receptacle to landfill by Waste Management, 3165 Northport Road, Tupelo, MS 38801.

b.  Full red rigid sharps containers are collected by housekeeping staff and presented for pickup by GreenServ.  Regulated medical waste is ultimately delivered by GreenServ to the incinerator to be properly destroyed.

5.  At study close-out visit, per sponsor request, all unused lab kits will be broken down and disposed of in a “red, rigid biohazard sharps container.” 

Biologic Specimen Collection, Storage, and Shipping Procedures:
Study-specific lab supplies will be provided to Cardiology Associates Research, LLC by study sponsors in order to obtain protocol required biologic specimens. Supplies provided should include, but not limited to: laboratory manual, quick reference chart, visit-specific laboratory kits, extra lab supplies, patient requisitions forms, packaging and shipping materials (i.e. boxes, pre-printed airbills, labels, etc.) and laboratory re-supply forms. Lab supplies will be stored in a dry, temperature-controlled area away from general patient population.

Research staff trained and licensed to perform phlebotomy should become familiar with the lab kit supplies, order of draw, and sample processing instructions prior to collection. Staff will ensure expiration date of kit prior to collection; complete required requisition forms for each specific kit/visit with the patients study ID; perform phlebotomy using universal precautions; universal precautions are also to be used when collecting other biologic samples such as urine, sputum, etc.

Centrifugation/processing of specimens will be performed per study-specific requirements as outlined in each study laboratory manual. Once processed, specimens are to be stored per protocol requirements and packaged/shipped per IATA guidelines and during the time frame indicated by each study. All research staff members involved in the collection, processing, and shipping of biologic samples are to complete and maintain IATA certification in accordance with GCP/FDA regulations. Staff certificates of completion are to be filed in the study regulatory binder or laboratory manual.

Study-specific lab specimens that are collected at North Mississippi Medical Center (hospital) that require shipment to an outside Central Lab will be processed by the appropriate licensed and trained research staff.  Once specimens are processed, the staff will prepare specimen according to IATA guidelines for shipment to the Central Lab facility and placed in the designated area for overnight courier pick-up.  If the specimen is obtained late in the day and the overnight courier has already made the scheduled pick-up, the research staff will then transport the shipping container by private vehicle to the nearest designated overnight courier location for drop off. 

 For specimens collected at the hospital for studies conducted at our outpatient clinic located at 499 Gloster Creek Village, Suite A-2, those specimens will be processed and prepared for shipment according to IATA guidelines for shipment to the Central Lab facility and placed in the designated are for overnight courier pick-up.  If shipping containers and documents required per study protocol are not available at the hospital office, the specimen will be placed in an appropriate biohazard container to prevent the possibility of spills, leakage, odors or spoilage and transported to the clinic for processing by the clinic research staff.   Study-specific lab specimens collected at the outpatient clinic will be processed by the appropriate licensed and trained research staff.  The staff will prepare specimen according to IATA guidelines for shipment to the Central Lab facility and placed in the designated area at the clinic for overnight courier pick-up. If the specimen is obtained late in the day and the overnight courier has already made the scheduled pick-up, the research staff will then transport the shipping container by private vehicle to the nearest designated overnight courier location for drop off. 

 For specimens collected at the outpatient clinic for studies conducted at the hospital, those specimens will be processed and prepared for shipment according to IATA guidelines for shipment to the Central Lab facility and placed in the designated area for overnight courier pick-up.  If shipping containers and documents required per study protocol are not available at the outpatient clinic, the specimen will be placed in an appropriate biohazard container to prevent the possibility of spills, leakage, odors or spoilage and transported to the clinic for processing by the clinic research staff. 

Storage of specimens is to be carried out as indicated by each particular study. All refrigerator/freezer units should be regularly inspected and kept clean. Food and beverages for human consumption will not be stored in refrigerators/freezers designated for biologic samples. All samples being stored in refrigerator/freezer will be appropriately labeled and will be placed in an appropriate container to prevent the possibility of spills, leakage, odors, or spoilage. Daily temperature logs (Monday-Friday) will be maintained for each refrigerator/freezer documenting daily temperatures. Temperature logs are to remain in close proximity to the corresponding refrigerator/freezer unit.

All source documents for each specimen (i.e. shipping airbill receipt, copy of sample requisition form, test result reports, critical values received via fax, etc.) are to be filed with other source documents generated for that visit in the patient shadow chart.

Study Close-out:  Once a sponsor has notified our site of study closure, the trial will remain active with the governing IRB, local or central, until all activities are complete.  This includes, but is not limited to, all queries resolved, all administrative/regulatory issues resolved, eCRF database is locked, final financial disclosures obtained, etc.  In the event annual renewal of the trial is required by the local IRB during the close-out phase, the trial will be renewed in order to remain active and the sponsor will be required to pay annual renewal fees based upon terms of the executed CTA.

Once a study has been officially closed with the local/Central IRB, a close-out visit has been completed and all documents archived, should a sponsor make a request for additional documents to be collected, a fee of no less than $300 will be assessed.  In the event of a substantial request for documents, the fee will be increased accordingly. 

Long-Term Storage of Research Documents: As individual trials close with both the sponsor and the governing IRB, all trial related documents (including, but not limited to: source documents for each subject screened/enrolled into the trial, contents of all regulatory binders, investigational product accountability logs, financial documents, etc.) are archived and stored in locked, secure storage located at Cardiology Associates of North Mississippi outpatient clinic at 499 Gloster Creek Village, Suite A2, Tupelo, MS 38801.  Archived documents are stored indefinitely or until Cardiology Associates Research, LLC receives notification from the sponsor or FDA allowing destruction of records.

Source Documents: Source documents include, but are not limited to hard copies of medical records such as History/Physical, consult notes, lab reports, radiology reports, EKG’s, operative notes, procedure reports, etc. These records are filed in a shadow chart for each individual subject.  Cardiology Associates Research, LLC uses two separate eMR’s—the eMR for the hospital facility, North MS Medical Center is SCM and the eMR for our outpatient clinic is EPIC.  Sponsors, monitors, or representatives of the trials are granted read-only access to SCM in order to monitor the subjects MR.  Access is not granted for EPIC—copies of records from EPIC are printed and filed in the shadow chart.  Prior to review of eMR records, Confidentiality Agreements for both NMMC and CARe must be signed.  Both eMR systems are CFR Part 20 compliant. (Please reference North Mississippi Medical Center EPIC Security Document.)

In the event of a Remote Monitor Visit request, a list of requested documents to be reviewed will be supplied by the sponsor.  Subject source records will be de-identified for all subject identifiers and uploaded via a secure sponsor web portal in the EDC or sent via an encrypted email.

Certified copies:  Cardiology Associates Research, LLC, as a means to certify source documents as a certified copy of the EMR, will stamp a group of stapled documents with a stamp that states “Certified Completed Copy of EMR From ____ To _____” signed by PI and dated.

In order to certify records from outside facilities, a Note to File will be included with such records declaring that they are a totality of what was received.  **Please note this policy is effective 02/01/2023.**

Vendor Representatives: Clinical trials conducted at North MS Medical Center facility often request or require a sponsor representative or vendor to be present during the treatment of a subject enrolled in a clinical trial.  All sponsor representatives and vendors entering North MS Medical Center for the purpose of supporting the treatment provided through a clinical trial must comply with North MS Health Services, Inc. Policy #955-02 and requirements of Reptrax.  Sponsor representatives and vendors can visit www.reptrax.com for a complete list of requirements and to complete registration and credentialing.  Sponsor representatives and vendors will be required to check in at the Reptrax kiosk prior to initiating any activities. (NMMC Policy #955-02 attached)

Routine Maintenance of Equipment: Medical equipment used to collect data points related to clinical trials are inspected and approved by North MS Medical Center Biomedical Department prior to the initial use of the equipment.  Routine maintenance and calibration for all medical equipment occurs at least annually.  Medical equipment includes but not limited to: digital and manual weight scales, automatic blood pressure monitors, EKG machines, lab centrifuge, IV infusion pumps, etc.  Records documenting initial and annual maintenance are kept in the Biomedical Department and are available upon request.  Labels can also be found on each piece of equipment documenting the month/year of the most recent inspection or maintenance. 

Emergency Provisions: (Note: this is the Emergency Response Policy for Cardiology Associates of North MS, Policy #366).   Any staff member who discovers a patient, visitor or employee in need of emergent care is responsible for getting appropriate assistance.

• Designated staff in each location are aware of the procedure to follow in their specific location. Crash carts are readily accessible.
• In the Tupelo clinic, the following procedure is to be followed:

1. • The staff member will seek assistance from clinical personnel in the immediate area.
   • A designated person in the room will call 911 and inform them of the location.
   • One person will be assigned to the entrance door to meet ambulance personnel and direct them to the emergency location.

• An RN and/or physician from the clinic may be asked by the ambulance crew to accompany the patient in the ambulance depending on the patient’s stability.

A copy of the resuscitation attempt form and/or other documentation should be sent with the patient. The physician and/or clinical staff will communicate as needed with the Emergency Room physician regarding the patient’s condition.

Billing:  CMS has issued a National Coverage Determination which addresses clinical trial services that qualify for Medicare coverage. The Regulatory Specialist will maintain documentation to support our involvement in such trials. Services specifically required for the research study outside the standard of care should not be billed.

The Regulatory Specialist checks the EPIC billing system on a daily basis for all enrolled research patients’ charges to determine if charges are billable to patient / insurance or not billable. 

References: CANM Policy #758, CANM Policy #761, CANM Policy #770

Mississippi State Board of Medical Licensure, Administrative Code, Title 30: Part 2640 (www.msbml.ms.gov)

North Mississippi Medical Center EPIC Security Document

POLICY DESCRIPTION: Clinical Research
POLICY #: 350
APPROVED: April 19, 2000
REVISION DATE: July 24, 2001
May 21, 2002
Nov. 21, 2002
March 19, 2003
July 22, 2004
August 10, 2005
September 6, 2007
January 16, 2008
August 14, 2008
November 17, 2009
February 10, 2010
August 12, 2010
November 9, 2011
March 4, 2014
September 10, 2014
July 7, 2015
March 10, 2016
May 13, 2020
September 16, 2021
August 10, 2022
March 29, 2023
EFFECTIVE DATE: June 1, 2000