Jacksonville – IRB-03 / Addendum NData Safety and Monitoring Plan
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Study Title:
The purpose of this document is to help you assess potential risk to subjects and develop a monitoring plan to protect subject safety and data integrity. Monitoring should be commensurate with level of risk, size and complexity of study. Blue1signifies increasing risk; an independent monitor may be needed. Red2 signifies high risk; a Data Safety Monitoring Board is strongly recommended or may be required. The Plan must be approved by the IRB.
Section 1: Risk related to Study Design
Risk and Complexity increase from left to right. Check appropriate answers.
Research Design / Observational / Intervention, but not intended to treat a disease / Treatment of a disease1Clinical Trial Design / N/A Placebo / Randomization1 / Blinding2
Trial Phase / N/A Phase I / Phase II / Phase III2
Number of sites / Single site / Multiple sites2
Possibility of major morbidity or mortality (either as endpoints or due to adverse events) / No / May be at risk for morbidity or mortality even if lesser outcomes such as relief of symptoms are addressed1 / Yes2
Investigational drug, device, or biologic (includes marketed drug used “off-label”, new formulation, dose, route, indication, population, or combination of drugs) / No / Yes1
Investigator holds an IND* or IDE** (becomes the sponsor) / No / Yes2
Assessment of serious toxicity requiring comparison of rates / No / Yes2
Safety data available / Yes / Limited early data available / None2
Potential for breach of confidentiality or invasion of privacy / Low
(Ex: No sensitive data; Computer secure. All paper records locked) / Moderate
(Ex: Some sensitive data. Office door usually open) / High1
(Ex: Sensitive data. Computers in clinical area and people nearby)
Research experience of PI / >2 years / 1-2 years / <1 year
* Investigational New Drug (FDA) **Investigational Device Exemption (FDA)
1Increasing risk - independent monitor may be needed
2High risk - a Data Safety Monitoring Board is strongly recommended or may be required
Section 2: Risk related to Study Population
Risk increases left to right. Check all appropriate answers.
Vulnerability of study subjects / Healthy Volunteer / Person with disease; able to sign consent / Vulnerable Child; terminally ill; frail elderly, mentally impaired, persons too sick to give consent2Severity of pre-existing disease or
condition / N/A Low / Moderate / High2
Section 3: Adverse events
Physical, social, psychological, or financial events that are anticipated due to subjects’ pre-existing disease.
Expected AE due to Underlying Disease / Likelihood of event occurring * / If event occurs, likely to be Serious*? / Plan:Examples: Chest pain / High (>10%) / Possibly / Treat AE as indicated; report AE to all required groups
MI / Low (<1 %) / Yes / Treat; Report
Anxiety / Moderate (5%) / Possibly / Treat; Report
*Use FDA definition of serious – death, life-threatening, hospitalization, disability/incapacity, birth defect
Addendum N: Data Safety Monitoring PlanPage 1 of 4
IRB Version: 11/24/09
PI Version:
Section 4: Risk Related to Research InterventionExpected risks due to the study are listed in the protocol. Refer to those risks to answer this question. The examples below are not comprehensive but are intended to provide guidance. Many studies will include elements from several different risk levels. In that situation, choose the highest level to which your subjects will be exposed.
Level / Risk / Study Procedures1 / No greater than minimal riskThe probability and magnitude of harm or discomfort anticipated in the research are not greater than those ordinarily encountered in daily life or during the performance of routine physical and psychological examinations or tests. / Blood draw, ECG, physical exam, standard psychological testing; epidemiological studies; use of otherwise discarded tissue obtained during a clinical procedure for clinical purposes only; behavioral study or nutritional assessment; surveys or questionnaires of a non-sensitive nature. Chart review. Use of already-developed database. Use of banked specimens.
2 / Low Risk
Study is non-therapeutic and interventions involve only a minor increase over those ordinarily encountered at a physician or psychologist’s visit OR the study is therapeutic but the agent to be studied has a known safety profile and is to be used for an indication and population already approved by the FDA. Expected adverse events are of low severity and reversible with low chance of serious harm / Well-described, short-term treatments to relieve common symptoms with known safety data at a single site; trials with procedures such as indwelling catheter, endoscopy, lumbar puncture, bone marrow biopsy, oral glucose-tolerance test, induced sputum, skin biopsy, imaging studies, collection of sensitive information; therapeutic trials of an agent already approved for use in the population to be studied and for the indication already approved at a single site.
3 / Moderate risk1Moderate to high probability of adverse events due to study intervention. Adequate surveillance and protection safeguards in place to identify and minimize effects of adverse events. Vulnerable subjects included. / Vulnerable subjects if interventions are no greater than minimal or low risk. Subjects with disease exposed to placebo; therapeutic intervention trial involving procedure such as insulin clamp or organ biopsy. Studies involving subjects with illness being treated with procedures that may result in moderately severe adverse events.
4 / Significant risk2 Study risk is greater than moderate due to the increased probability for generating serious adverse events. High probability of an adverse event that is serious and prolonged or permanent occurring as a result of study participation or there is much uncertainty about the nature or likelihood of adverse events. / Clinical trials of diseases where the endpoints are major morbidity or mortality; assessment of serious toxicity requiring comparison of rates; implantation of a device with an IDE; use of a new chemical or drug for which there is limited or no available safety data in humans; gene transfer; multi-center trials involving risk to subjects; high-risk clinical procedure if performed solely for research purposes
Section 5: List your sources of information about risk Check all that apply
Earlier studies (animal) / Earlier trials (human)Investigator’s Brochure / Package insert
Other:
Section 6: Determination of Overall Risk Level
Overall risk level is based on the factors described above in Sections 1 through 5 on study design, population being studied, and potential harms from participation in research. Considering all of these factors, the potential for harm to subjects in this study is
No more than minimal Low Moderate1 Significant2
Section 7: Who will assess safety and data integrity for your study?
Principal Investigator (required for all studies)
Institutional Review Board (IRB – required for all studies)
Independent Individual/Medical Monitor1
Internal Data and Safety Committee or Board with explicit guidelines2
Independent Data and Safety Monitoring Board (DSMB). NIH specifically requires the establishment of Data and Safety Monitoring Boards (DSMBs) for multi-site clinical trials involving interventions that entail potential risk to the participants, and generally for Phase III clinical trails. Although Phase I and Phase II clinical trials may also use DSMBs, smaller clinical trials may not require this oversight format, and alternative monitoring plans may be appropriate.
Section 8. Study Wide Monitoring Frequency
How often will the safety and data integrity of accumulating study-wide data across all subjects be monitored? Example: After first 3 subjects have completed intervention; every six months; yearly
Has a safety endpoint been established?
N/A
No
Yes – describe:
Has an efficacy endpoint been established?
N/A
No
Yes – describe:
Have stopping rules been established?
No
Yes – describe:
Section 9. Other Assessments
a. WHAT will be assessed?
Reports of your safety assessments must be sent to the IRB and any other appropriate entities such as, Independent Monitor, and/or DSMB at time points selected by you in Section 8 above.
b. Individual Subject Safety: List planned assessments and who will be responsible.
Specify any special conditions under which assessments are to be made or special equipment to be used. Provide specific lab alert values or other clinical criteria that would lead to alteration or discontinuation of a subject’s participation. Add rows as necessary.
Addendum N: Data Safety Monitoring PlanPage 1 of 4
IRB Version: 11/24/09
PI Version:
Safety Assessment / Special conditions/equipment Criteria leading to alterationor discontinuation of subject participation / Personnel responsible for assessment
Examples: Resting blood pressure measurement / Manual cuff. 15 minutes of rest prior to BP measurement.
Must be <180/99 to continue / Shands nurses perform BP measurement and notify PI or study staff as written in the orders
Pregnancy test / Urine test done in Shands lab.
If positive, S is withdrawn / Designated Lab Technologist runs test. Study Coordinator or PI withdraws subject
Hepatic panel / If ALT >2x upper limits of normal, decrease dose by 50% / Drawn by clinical staff. Result checked by Study coordinator or PI
Telephone call to subject after discharge from hospital / Within 24 hours If c/o pain, bring subject in. Notify PI / Study Coordinator
c. Data Quality and Confidentiality
- How will you check accuracy and quality of collected data?
- Were there any breaches of confidentiality?
d. Regulatory Compliance
- If your study is sponsored, will the sponsor send a monitor?
Yes
No -
- Will you keep a Regulatory Binder?
Yes -
No
e. Evaluating and Reporting Adverse Events
- Who will evaluate adverse events for seriousness, expectedness, severity, and relationship to study intervention?
- What definitions will you use?
If no definition is provided by the sponsor’s protocol, the following definition may be used: Any untoward occurrence (physical, psychological, behavioral) that occurs during the course of the study regardless of its causal relationship with the intervention/procedure/treatment being studied.
- What grading scales will you use to evaluate adverse event seriousness, severity, and relationship to study interventions?
If definitions are not specified in your protocol, you may consider adopting these:
SeriousFDA definition: A serious adverse event
results in death,
is life-threatening,
requires inpatient hospitalization or prolongation of existing hospitalization,
results in persistent or significant disability / incapacity,
results in a congenital anomaly / birth defect.
Severity:
Severity describes the intensity of a specific event and is graded from 1 (mild) to 5
(death). It is highly recommended that you use NCI Common Terminology Criteria for Adverse Events v3.0 (CTCAE) If that system doesn’t seem appropriate for your study, you can use
Mild: easily tolerated, causing minimal discomfort
Moderate: sufficiently discomforting to interfere with every day activities
Severe: prevents normal every day activities
Relationship:
Unrelated: There is no association between the study intervention and the reported event
Related: A definite causal relationship exists between the event and the study, and other conditions (concurrent illness, progression of disease or concomitant medication use do not appear to explain the event).
Cannot be ruled out: The event might be related to the intervention, but could also have been produced by other factors
- To which committees/agencies will adverse events be reported? (Check all that apply)
IRB (required)
NIH Institute or Center sponsoring your study Industry sponsor
FDA (if you hold an IND or IDE) DSMB
DSMB
NIH Office of Biotechnology Activities (for gene transfer studies)
Other: Specify
- Who will treat adverse events?
Addendum N: Data Safety Monitoring PlanPage 1 of 4
IRB Version: 11/24/09
PI Version: