Data and Safety Monitoring Plan

Data and Safety Monitoring Plan

The National Institutes of Health (NIH) policy statute that all studies performed in the Puerto Rico Clinical and Translational Research Consortium (PRCTRC) must have a Data and Safety Monitoring Plan (DSMP). The PRCTRC has developed a DSMP that outlines appropriate oversight and monitoring of research that includes all types of intervention in studies, whether medication or non-medication trials (e.g., behavioral, prevention, diagnostic). This is to ensure the safety of participants, the validity and integrity of the data. The specific study plan will depend on the nature, size, complexity and risk of the research study. An external Data and Safety Monitoring Board (DSMB) is required for multi-site clinical trials involving interventions that involve potential risk to the participants.

All investigators must submit a DSMP and/or DSMB (if applicable) when requesting support from the PRCTRC. The Research Subject Advocate (RSA) is available to assist investigators and coordinators in identifying, developing, and overseeing risk-appropriate monitoring plan. Before human subject research can begin, the DSMP will be reviewed as follows: As a first step, the Regulatory Knowledge and Support (RKS) Core leader will review and approve the DSMP. As a second step, the RKS Core leader will inform the PRCTRC Internal Advisory Committee (IAC) of his/her decision.

The purpose of this plan is to develop a prospective strategy:

·  To monitor the safety of the participants enrolled in the study

·  To assess whether the trial should continue as planned, whether changes to the protocol are necessary, or whether participants should be notified of new findings

·  To examine the total adverse event experience at designated intervals.

The required elements of a DSMP for a study are dependent on the magnitude of risk to which research subjects are exposed all must address:

·  Study risk assessment

·  Adverse event grading and plans for reporting adverse events

·  Description of whom will be performing the safety reviews

·  Description of safety monitoring plan to assure:

o  Only subjects who meet the study eligibility criteria are enrolled

o  The informed consent process is conducted appropriately and that informed consent is obtained prior to proceeding with any study procedures;

o  Data is collected and analyzed as specified in the protocol;

o  Adverse events are reviewed promptly and reported as required; and

o  Privacy and confidentiality of study subjects is maintained.

Study Title:

Principal Investigator Name:

Protocol IRB#:

I-DESIGN (Select all that apply):

Multicenter
Randomization of treatment assignment
Blinding Single Double
Placebo control
An investigational drug, device, or other substance will be utilized. (This includes a marketed drug that is used “off-label”, for example, a different formulation, and dose, route of administration, Indication, population, or combination of drugs than what is approved by the FDA.)
Investigator holds the Investigational New Drug (IND) application or the Investigational Device Exemption (IDE) (the PI is then an investigator/sponsor)
Observational study:
Other, specify:

II-DETERMINING LEVEL OF RISKS

A- Subjects (Select only one):

Low Risk - healthy participant. Adults able to understand risks and benefits and to sign consent.
Moderate Risk – ill population. Adults with a disease or condition; able to understand risks and benefits and to sign consent; other treatment options available OR Vulnerable subjects (children, prisoners, pregnant women and their fetuses, elderly, institutionalized).
High Risk - seriously ill population. Vulnerable subjects (children, prisoners, pregnant women and their fetuses, elderly, institutionalized), OR subjects are unable to understand risks and benefits, cannot make decisions on their own, and cannot sign consent, OR subjects are critically ill patients with no other treatment options available

B- Procedures/Interventions (Select all that apply):

When determining this risk, think about the possibility of harm and consider both the magnitude of harm (from transient discomfort to death) and the probability that harm will occur (unlikely to highly likely). Risk may be psychological, social, or legal as well as physiological. Remember to consider the research interventions only. Procedures that are standard of care that the subject would undergo whether in or out of the study should not be part of the risk consideration.

Safety Level 1 – Minimal Risk means that the risk of harm anticipated in the proposed research is not greater, considering probability and magnitude, than that ordinarily encountered in daily life or during the performance of routine examinations, tests and treatments that might occur during a routine visit to a physician.

Physical/dental exam / Electrocardiograms (EKGs)
Pregnancy test / Ultrasound/CT scan/MRI/Single X-ray (non-contrast)
Urine collection / Pulmonary function tests (PFTs)
Anthropometric evaluations / Pathology slide review
Special/prescribed diets / Observational/neuropsychological/ neurocognitive studies
DEXA scan / Venipuncture < 200 mls of blood
Exercise testing / Intravenous catheter insertion < 24 hours
Survey/Questionnaires / Drug/Device used for FDA approved labeling
Dietary assessment / Simple/Punch skin biopsy
Herbal supplement to healthy subjects / Oral/IV Glucose tolerance test
FDA approved drug/device with low side effect profile / Other Level 1 risk, specify:

Safety Level 2 – Moderate Risk means that the risk of harm anticipated in the proposed research is somewhat greater than that encountered in a routine visit to a physician.

Venipuncture with removal of 200-500 ml blood / Endoscopy
Intravenous catheter insertion > 24 hours / Cardiac stress test
Intravenous drug administration / Genetic testing
Ultrasound/CT scan/MRI (standard contrast agents) / Use of FDA approved drug for non-approved indication (off label)
X-ray or other ionizing radiation (multiple exposures) / Lumbar puncture
Device study / Herbal Supplement with moderate side effects or to ill subjects
Withholding medications/washout / Biopsy (e.g., skin, muscle, fat)
Investigational drug –Phase II/III / Investigational device – nonsignificant risks
Other Level 2 risk, specify:

Safety Level 3 – High Risk means that the risk of harm anticipated with the proposed research is substantially greater than that encountered during a routine visit to their physician.

Gene transfer study
Investigational drug – Phase I/II
Transplant (cells, tissue, solid organ)
Venipuncture with removal of > 500 mls blood)
Investigational devices – with significant risks
Other Level 3 risk, specify:

C-Overall level of Risks

Identify the overall level of risk of this study, which will determine the frequency of safety monitoring. This level must be the same as the highest level checked in the previous section.

Low
Moderate
High

III-MONITORING PLAN

NIH already requires Data and safety monitoring, generally, in the form of DSMB for phase III clinical trials. For earlier trials (phase I and II), DSMB may be appropriate if the studies have multiple clinical sites, are blinded, or employ particularly high risk interventions or vulnerable population. It is the prerogative of Regulatory Knowledge and Support Core to require the DSMB for phase I and II.

A-Safety Monitoring

1.  Who will monitor this study? Indicate who will be performing the safety monitoring of research subjects study (Select all that apply)

The PI will perform safety monitoring
A medical monitor or independent individual/safety officer will be performing the safety monitoring. Please complete table below. This person will be a licensed physician who is not directly involved in the study, has no financial interest in the study outcome, and is not collaborating with the sponsor/investigator in any study.
Name / Position / Role on project
An internal DSMB will perform the safety monitoring. None of the board member should be affiliated with the study. If selected, a description of the board must be provided to the Key function leader of the RKS. This description should include: (Use a separate sheet)
·  A list of the board members.
·  The frequency with which the study will be evaluated.
·  Adverse event reporting procedures.
·  A description of how interim analyses will be performed.
·  A list of the study stopping rules.
·  A list of who will receive DSMB reports.
An external DSMB provided by the sponsor or agency will perform the safety monitoring. If selected, a description of the board must be provided to the Key function leader of the RKS. This description should include: (Use a separate sheet or provide copy of the sponsor or agency DSMB)
·  A list of the board members.
·  The frequency with which the study will be evaluated.
·  Adverse event reporting procedures.
·  A description of how interim analyses will be performed.
·  A list of the study stopping rules.
·  A list of who will receive DSMB reports.

2.  How often will data and safety be monitored? The frequency of the safety review is dependent upon the risk of the trial. Regardless of the risk level, it is expected that study investigators will review safety data on each subject real-time to protect that individual safety. Safety reviews (or interim analyses) should be conducted as often as needed, based upon the risk level and the speed with which subjects are enrolled.

Annual at the time of IRB continuing review
Every months
Every subjects
Other, specify:

3.  Check the specific information to be monitored and provided in a report to the PRCTRC and IRB at the time of each continuing review. Select those appropriate for your study, add additional items as needed:

Enrollment
Drop-outs
Adverse events reviews
Protocol Violations/Deviations
Efficacy reviews (specify outcomes to be evaluated):
Other, specify:

4.  Confidentiality:

Discuss how data confidentiality will be maintained: Please indicate your plan to protect the private health information from improper use and disclosure (e.g., assign study numbers, de-identification process, locked storage).

5.  Data integrity and security:

Describe how data will be organized, managed, and stored. Security measures used to protect study data from loss or inappropriate use. (e.g., password protection, restricted access to database, database backup)

6.  Informed consent process:

Describe your plan to assure that the consenting process will be conducted properly and in accordance with all federal regulations.

7.  Which are the predetermined criteria (stopping rules) for stopping or modifying the study (e.g., endpoints of the study)?

IV-ADVERSE EVENT REPORTING

A- Definitions of Adverse Events:

Definition of Adverse Event (AE): any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporarily associated with the use of a medical treatment or procedure regardless of whether it is considered related to the medical treatment or procedure.

·  Anticipated (Expected) Adverse Events: these are risks or events reported in the Investigator’s Brochure and listed in the consent form. The IRBs and the PRCTRC will consider an adverse event as “anticipated” or “expected” only if it is discussed in the Investigational Brochure, protocol and included in the Informed Consent document.

·  Unanticipated (Unexpected) Adverse Events: an unanticipated adverse event is any unexpected untoward event or medical occurrence in a study subject that is not consistent with the known, predicted possible effects of the research protocol. An unanticipated adverse event can therefore be any unanticipated, unfavorable, and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the study that was not listed in the protocol, consent form or investigator’s brochure. This includes any experience that suggests a significant hazard, contraindication, side effect, or precaution. In addition to this definition, the IRBs and the PRCTRC interpret any adverse event not included in the Informed Consent document as a risk to be “unanticipated” or “unexpected.”

Definition of Serious Adverse Event (SAE): A serious adverse event (SAE) is defined as an adverse event that results in any of the following outcomes:

·  death

·  life-threatening event (an event that places the patient or subject, in the

·  view of the investigator, at immediate risk of death from the experience)

·  inpatient hospitalization or prolongation of existing hospitalization

·  persistent or significant disability/incapacity

·  congenital anomaly/birth defect

B-  Identification of Adverse Events

Indicate how adverse events will be identified (Select all that apply):

Interviewing subject
Physical exam
Spontaneous report from subject
Laboratory results, specify:
Safety tests, specify:
Other, specify:
Not applicable

C-  Grading Methods for Adverse Events

Investigators are encouraged to use a standardized scale to grade AE’s by severity. There are several available designed for disease-specific trials, but are generalizable to other studies. Indicate which scale will be used to grade AE’s:

Standardized adverse event, please describe:
Not Applicable

D- Attribution of Adverse Events Categories

Indicate a scale to be used by the PI to attribute the relatedness of the experience to the study procedures/interventions:

Three points attribution scale: Related, Possibly related, and Not related.

Five-point attribution scale: Definitely related, Probably related, Possibly related,

Probably not related, and Definitely not related.

Other attribution scale, please describe:

Not Applicable

E- Reporting of Adverse Events

Adverse event(s) must be reported within a specific time frame to the corresponding IRB using the applicable report form. A copy of all reports submitted to the IRB and /or other entities must be sent to the RKS Core and to any of the following: (select all that apply)

NIH Institute or Center sponsoring your study

Industry sponsor

FDA (if you hold an IND/IDE or the FDA sponsors your study)

DSMB

Other, specify:

Not Applicable

V- SIGNATURE:

By signing above the PI agree to adhere to the following terms:

A.  The PI assures that the consenting process will be conducted properly and in accordance with the federal regulations.

B.  The PI assures that the actual conduct of the study, record keeping, data collection and processing by the research personnel will be monitored during the study.

C.  The PI affirms that research personnel associated with the study have completed the Human Subject Protection, HIPAA and the Good Clinical Practice trainings.

D.  The PI affirms that adverse events will be reported to the MSC IRB, PRCTRC and appropriate entities.

E.  The PI affirms that he/she has read the PRCTRC Code of Ethical Conduct .

Study Title:

Principal Investigator’s Name (print) / PI signature / Date (mm/dd/yy)
RKS Leader’s Name (print) / RKS Leader signature / Date (mm/dd/yy)
Recommendation:
Approve DSMP
Approve DSMP contingent to modifications
Do not approve DSMP

1 | RKS

DMSP Template

Revised 12.06.16