Clinical and Translational ResearchCenter AddendumVersion: 6/29/2011

CTRC Addendum to the IRB Application

If you plan to use a CTRC Facility and any of its many services and resources, please complete the form below. The success of your study is important to us and it is imperative that you outline carefully what you need so that the CTRC Staff are ready and able to meet those needs.

  • Along with the completed addendum, include the billing and cost assignment sheet, contract, budget and, if appropriate, time and event worksheet/flow sheets.
  • Provide us with your study’s IRB application, industry or master protocol, and investigator brochure.
  • Instructions are highlighted in yellow. You may delete both highlighted text and sections regarding optional services that you are not using prior to submitting this addendum.

CTRC Protocol Number

Title of Study:

Protocol Version Date:

Principal Investigator:

UNC Medical Staff Appointment Yes No

Telephone #: Pager #: Email Address:

Study Coordinator:

UNC Medical Staff Appointment Yes No

Telephone #: Pager #: Email Address:

Main Nurse Practitioner/PA (if applicable):

UNC Medical Staff Appointment Yes No

Telephone #: Pager #: Email Address:

*Study Physician (if not Principal Investigator):

UNC Medical Staff Appointment Yes No

Telephone #: Pager #: Email Address:

*Medical orders and physician oversight are required when research participants are admitted to the CTRC.

Check ALL services you plan to use

/ REQUIRED SECTIONS FOR ALL PROTOCOLS / SECTION to complete
/

Safety Monitoring Plan

/ A
/

Biostatistics and Database Management

/ B
/

Cost Determination and Assignment

/ C

OPTIONAL CTRC SERVICES

/ Study Medication or Investigational Agent Administration / D
/ Outpatient clinical services (CTRC at UNC Hospitals) / E
/ Outpatient clinical services (CTRC at Burnett-Womack) / E
/ Inpatient admissions (CTRC at UNC Hospitals) / F
/ Meals: Research diets, regular meals and/or nourishments / G
/ Research Nutritionist services / G
/ Body Composition Measurements / G
/ Dental Research: GeneralOralHealthCenter / H
/ Specimen Processing Facilities and Sample Storage / I

Section A. Safety Monitoring Plan(Revised June 23, 2009):

All CTRC and TraCS supported protocols require a protocol-specific Safety Monitoring Plan (SMP). Providing the answers to the questions below will formulate a SMP that is specific for the study. The SMP can then be used by your study team as a guide when implementing and monitoring the protocol. Please read and answer each question carefully and completely. If the requested information can be found in the protocol and is too large to cut and paste into this form, you may reference the page number(s) and section(s) where the information is located. For information or assistance in writing a Safety Monitoring Plan, contact David Weber, phone 843-0725, or Marie Rape, phone 966-6844 .

  1. What is the level of risk to subjects for this protocol? Please refer to theProtocolRisk Assessment and MonitoringGuidelines to assist you in determining and justifying the Risk Level.

SELECT ONE:

Level 1: No greater than minimal risk--Non-interventional or risk no more than experienced in daily life (e.g., blood draw, physical exam, MRI, exercise testing)

Level 2: Minor increase over minimal risk

Level 3: Moderate risk

Level 4: High risk

AND

For Risk Levels 2-4: In a few sentences, please justify risk level:

  1. What tests, evaluations, or observations will be performed to monitor subjects and minimize risks? Provide us with a visit table, schedule of events, or list of specific tests and evaluations that will be used, and their frequency, to assess subjects and monitor for toxicity. Describe any other measures in place to minimize risk.
  1. Which classification scale will be used to grade the severity of adverse events (AE)? For protocols that do not have a specific grading scale, the most recent Common Terminology Criteria for Adverse Events (CTCAE scale) is recommended. A scale of mild-moderate-severe (as defined below) may be used for simple studies.

NOTE: Although not anticipated, adverse events may occur in any study and should be tracked (whether or not they are reportable) and graded by the investigator or study physician. AE tracking templates can be uploaded from the OCT website.

SELECT ONE:

Adverse Event Grading Scale:

MildAdverse Event – Event results in mild or transient discomfort, not requiring intervention or treatment; does not limit or interfere with daily activities (e.g., insomnia, mild headache).

Moderate Adverse Event – Event is sufficiently discomforting so as to limit or interfere with daily activities; may require interventional treatment (e.g., fever requiring antipyretic medication).

Severeand undesirable Adverse Event – Event results in significant symptoms that prevents normal daily activities; may require hospitalization or invasive intervention (e.g., anemia resulting in blood transfusion).

Common Terminology Criteria for Adverse Events v3.0 (CTCAE)

Division of AIDS Table for the Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading table)

Other. Please describe or provide protocol reference:

  1. To whom and with what frequency will Unanticipated Problems and Adverse Events be reported?

PLEASE CHECK TO INDICATE YOUR UNDERSTANDING OF LOCAL REPORTING REQUIREMENTS

Reporting of Unanticipated problems and adverse events to the IRB (IRB SOP Section 19.0)

  • All NON-SERIOUS unanticipated problems and adverse events that are both unexpected AND related or possibly related to participation in the research will be reported to IRB within two weeksof the investigator becoming aware of the event.
  • All SERIOUS unanticipated problems and adverse events will be reported within one week of the investigator becoming aware of the event.
  • Upon review of the report, the IRB will make a final determination as to whether the event places the subjects or others at greater risk than previously recognized.
  • All reports will be submitted directly to the IRB.

AND

Discuss reporting of unanticipated problems and adverse events to the sponsor, FDA or NIH:

OR

There are no additional reporting requirements for this study.

Questions 5-8 pertain to studies with a research intervention (administering a medication, substance, or investigational agent; exposure to experimental conditions, etc.). Please mark N/A if not applicable to your study.

Not Applicable (no research interventions included in study)

  1. What are the subject stopping rules? List the specific reasons or adverse events (including grade or number) that would lead to a subject having the research intervention discontinued or put on hold. If there are any rules for dose escalation or de-escalation, please describe.
  1. Identify the committee or group responsible for monitoring or reviewing adverse events in aggregate across the entire study population for the protocol

SELECT ONE AND DESCRIBE

Single-center, Moderate Risk protocols, Phase I or II trial: This study requires a plan for aggregate analysis of adverse events.

Describe who (person or committee) is responsible for receiving and reviewing adverse events in aggregate across the entire study population; summarize how and at what intervals data will be reviewed.

OR

Multi-center, high-risk protocols or Phase III trials: This study requires a Data Safety Monitoring Board (DSMB) or Data Monitoring Committee (DMC) to monitor the protocol.

Describe the committee that will monitor this study; provide a copy of the charter or details of the membership and frequency of meetings. If a DSMB or SMC will not be utilized, explain why not.

  1. Are there any study-wide stopping rules for this protocol? Describe rules for when the entire study would be stopped (in all subjects) and re-evaluated for either safety or efficacy reasons.
  1. Who will monitor this study? Provide the name of the company or organization and frequency of any monitoring. If there is no outside monitoring, describe who will handle study documentation anddescribe your plans for performing quality control/assessment of source documents to ensure the accuracy of data collected.

SELECT ONE

Industry Sponsor or CRO monitor: (name) Frequency of monitoring:

OR

No outside monitoring—Internal self-monitoring will be performed.

At least 10% of individual case report forms and source documents will be reviewed to confirm that all recorded data is verifiable, accurate and complete. Areas to be assessed include informed consent process, subject eligibility, Case Report Form (CRF) and/or source document completion/accuracy, Adverse Event Reporting, and Drug Accountability (as applicable).

OR

No outside monitoring—Other Internal self-monitoring plan.

Please describe:

Section B. Biostatistics and Database Management

All CTRC applications should provide sufficient detail to allow useful biostatistical review. A master protocol is recommended for all studies.

If you have questions or if you would like a pre-review of your statistical plan, please contact Paul Stewart, , phone 966-7276.

For assistance in completing Database Management questions, contact Clarence Potter, , phone 966-4802.

  1. Does this study have a Master Protocol documentwith sections that completely specify the plans for data analysis and data management?
  2. Yes. Please submit the master protocol and list the appropriate page reference where this information can be found. IF all questions are completely addressed in the master protocol, you DONOT need to answers questions 2 – 5 below.

List page references: ______

  1. No. Please address questions 2 – 5. If you have access to a biostatistician, ask them to complete this section for you. If you do not have access to a biostatistician, please contact Paul Stewart for assistance in answering these questions.

If a particular question has been addressed adequately in the IRB Application or in the Master Protocol, you may reference that section rather than repeat the details in the box below.

  1. Characteristics: aims, study design, sample size, and randomization:
  2. What are the scientific aims and practical objectives of this study? (Examples: publication, get data for a grant proposal, pilot-test procedures, study feasibility, estimate parameters, generate hypotheses, test hypotheses, etc.)
  1. What were the primary considerations in choosing the proposed sample size? (Examples: stage of this line of research, specific aims, patient availability, costs, precision of statistical estimates, power of statistical hypothesis test)
  1. What is the plan for randomization (if any) and who will perform the computations? (Examples: stratified randomization, permuted blocks, constrained-block allocation sequences).)
  1. As used in the analyses, what will be the units and scales of the most important variables? (Examples: HIV viral load (l og10 copies/mL), CD4+ (count), Weight (kg), etc.
  1. Statistical analysis of the data
  2. Who will perform the statistical computations and who will analyze the results?
  1. For what parameters will statistical estimates be obtained? (Examples: proportions, medians, mean differences, variances, prevalence rates, etc.)
  1. What levels of precision are anticipated for the most important estimates? (Examples: expected width of confidence interval, expected magnitude of standard error, etc.)
  1. What are your plans for computing confidence intervals for these estimates?
  1. What hypotheses (if any) will be tested and what test procedures will be used?
  1. What is your strategy for controlling the probability of type I errors? (Example issues: multiple comparisons, rate of false discoveries, test size (), etc.)
  1. What levels of power are anticipated for each of the most important tests?
  1. Will this study be a success even if no tests are statistically significant?
  1. Database Management
  2. What are the plans for data management (RDM)? (Examples of aspects: data entry, quality assurance, data editing, data archival, etc.)
  1. How will you verify that the data has been entered into the database correctly? (Examples: quality assurance monitoring, double-entry, independent verifications, etc)
  1. What software will be used for database management?
  1. Who will perform the computations for data management? (Examples: data retrievals and numerical comparisons for monitoring, reporting, etc.)
  1. What are the plans for ensuring that custom-written algorithms, sub-routines, formulas, or macros perform correctly without error?

Section C. Cost Determination and Assignment

General Instructions:

The information you provide by completing theCost Assignment Sheet (see next page)will be used to determine resource utilization and cost of CTRC resources and to identify the person(s) responsible for specific costs.

Protocol Categorization:

Determination as to what extent a research project will be supported will be determined by the CTRC Oversight Committee. A research protocol is designated as one of the following categories:

Category B Studies Category C Studies Category D Studies

Study initiated by a Early-Stage Investigator (NIH/Grant, Foundation, Department sponsored, Network studies, or unfunded research) / Study initiated by an investigator (NIH/Grant,Foundation, Network studies, Department sponsored, or unfunded research) / Study initiated by an investigator or industry and sponsored by industry

Definition of Early-Stage Investigator:

A Principal Investigator is considered an “Early Stage Investigator” if he/she is within 10 years of completing his/her terminal research degree or is within 10 years of completing medical residency (or the equivalent).

Investigator-initiated Protocols:

Investigator-initiated studies are generally funded by a non-profit, state, or government agency; however in some cases, studies may also receive industry funding. For multi-center studies, UNC does not have to be the coordinating center; however; the researchmust meet all of the following criteria to receive a designation as an Investigator-initiated protocol:

  • The research is within the investigators’ area(s) of academic research interest.
  • The investigator(s) have had substantial input into protocol design for the proposed protocol and take responsibility for the quality of the protocol.
  • The principal investigator will have full control of the data and will be the responsible author for all major publications that result from the research.

IMPORTANT: For information or assistance in completing the Cost Assignment Sheet, please contact Leslie Powell, 919-843-0267, .

1

3/3/09

Billing and Cost Assignment Sheet: Please Read Instructions

Protocol Number: Title of Study:

Principal Investigator:

Telephone #: Pager #: Email Address:

Study Coordinator:

Telephone #: Pager #: Email Address:

Departmental billing /Cost Sheet contact:

Telephone #: Pager #: Email Address:

Is this study (choose one): *Investigator initiated Industry initiated
* Investigator-initiated studies must meet ALL of the four criteria listed in the instructions.
Are you (choose one) : *Early-Stage investigator *Senior investigator
*Refer to definitions in the instructions
Are you requesting Research on Location (CTRC staff comes to in-patient hospital or outpatient clinic setting)?
Yes No
Are you requesting the CTRC Dietary Services to prepare meals for your patients (please note that there is now a charge for each meal)?
Yes No
Please indicate ALL funding sources that will pay for this study (check all that apply):
Federal funds Industry funds Other (foundation, dept, etc.)
If Other, name funding source:
Are you applying for TraCS Pilot Funding? Yes No
If yes, have you received APPROVAL for funding? Yes No
If yes, FUNDING AMOUNT: $
Total number of subjects: Estimated duration of study (i.e., subject interaction): years
Number of outpatient subjects: Number of outpatient clinic visits/subject:
Number of inpatient subjects:Number of inpatient NIGHTS/subject:

REQUEST FOR TESTS, PROCEDURES, MEDICATIONS AND/OR SUPPLIES

Name of Test/Procedure (e.g., Lab, CXR, Dexascan, lidocaine, etc)
See exceptions below(1) / Number per Subject / Lab or Departmentperforming test
See examples below(2) / Test/Procedure billed to: (Check one)
Subject / Insurance / Investigator 98 Account / CTRC 3
  1. DO NOT list “kit” labs (i.e., those being sent to a Central lab) or other non-billable tests and/or procedures for which the Sponsor has provided you with materials and/or equipment.
  2. Examples: McLendon Labs, Investigator Lab, Body Composition, Cardiology, Pulmonary or Core Facility Labs.

PLEASE NOTE: “Core Lab” refers to UNC core facilities that provide support for clinical investigators, not McLendon Core Lab.

  1. CTRC should not be chosen for any study approved after September 1, 2009. No Costs will be paid for by the CTRC if approved after this date.

98 Account Number for Investigator charges: / 98#:
PI Signature: / Date:
CTRC Approval Signature: / Date:
Category of research for billing purposes (Designation to be made by CTRC): ______

Optional Services: Complete Section(s) Relevant to Your Study

Section D. Study Medication or Investigational Product Administration

You are required to register with the Investigational Drug Service (IDS) Pharmacy if your study involves the administration and dispensing of any agents (commercial medications, supplements, or investigational drugs/products). This policy is a JCAHO requirement and a means of assuring compliance with Federal regulations and quality control.Information regarding IDS services, policies and application forms can be obtained at

The Investigational Drug Service has two locations:

  • 3rd floor, MainHospital, Room 3001. Dispenses injectable medications and chemotherapy. Phone:966-3469.
  • Ground Floor Neurosciences, across from ENT clinic. Oral medications dispensed from this location. Phone: 966-8739.