OHRP Determination Letter Ellen Roche, a healthy volunteer, died as a result of her participation in a research study at John Hopkins. OHRP noted “the investigators and the IRB failed to obtain published literature about the known association between hexamethonium and lung toxicity.”
Writing an IRB Protocol Critical Points All research protocols expose participants to some degree of risk. The written protocol should support the results of a trial. If the protocol is poorly written, no subsequent analysis may be able to salvage the trial.
Why is a Protocol Important to the IRB The VU IRB requires a protocol for consistency in the review of research. A protocol serves as the reference point for review of a Health Science/Biomedical IRB Application.
Challenges Write a protocol to address all scenarios. Create an effective road map to guide anyone who may become involved with the trial. To stay within the parameters of the protocol (do only what you say you are going to do…not more or less). Make sure the study is scientifically sound and has statistical power.
Creating an IRB Protocol Identify the question the study will answer. Conduct a literature search. Identify any investigational agents/devices.
Title Page State the full protocol title. Provide the PI’s name and address. State who will be supporting the study. State the date of the protocol. Optional: Names of Sub-PI’s IND or IDE holder
Sample Title Page Protocol Title The Effects of Tagalong Peanut Butter Girl Scout Cookies: A Randomized Trial Principal Investigator’s name and address James Jones, M.D., Department of Medicine Vanderbilt University, 504 Oxford House, 4315 Sub-Investigators and their affiliations Jane Doe, M.D., Department of Medicine, Vanderbilt University Version Date April 23, 2013
Table of Contents Study Schema 1.0 Background 2.0 Rationale and Specific Aims 3.0 Animal Studies and Previous Human Studies 4.0 Inclusion/Exclusion Criteria 5.0 Enrollment/Randomization 6.0 Study Procedures 7.0 Risks of Investigational Agents/Devices (side effects) 8.0 Reporting of Adverse Events or Unanticipated Problems involving Risk to Participants or Others 9.0 Study Withdrawal/Discontinuation 10.0 Statistical Considerations 11.0 Privacy/Confidentiality Issues 12.0 Follow-up and Record Retention Appendices
1.0 Background Provide the history of the topic and why the research is important. Include any pertinent pre-clinical, pilot, and preliminary and/or unpublished data to support the conduct of the proposed study. Include information about the disease, the number of people it affects, and how it affects the population.
Background Over the past 8 decades, the number of boxes of cookies being sold by girl scouts has steadily increased. Although studies have been conducted by the Girl Scouts of America regarding what may motivate young girls to lead a healthier lifestyle (Schoenberg, 2006), research has not been conducted on the potential benefits or risks associated with the consumption of the cookies to determine its impact on the health of the American population. This study will examine how consuming the Tagalong peanut butter cookie affects glucose and cholesterol levels.
2.0 Rationale and Specific Aims State the hypothesis and scientific justification for conducting the study or why something which is widely accepted needs to be challenged (new information or findings). Be sure to justify the target population, endpoints, and why particular techniques will be used for endpoint assessment, measurement of drugs, drug effects, etc. Clearly differentiate the specific aims in order of importance.
Rationale and Specific Aims Each year, thousands of boxes of girl scout cookies are sold and consumed. However, the ramifications of subjecting the human body to sudden increases in sugar and fat has yet to be explored. The effect on heart disease, hyperglycemia, and weight gain needs to be examined to determine if warnings labels need to be added to the product packaging and to determine how long it will take for serum and cholesterol levels to return to baseline. Include information on diabetes, heart disease, etc.
Rationale and Specific Aims The specific aims will be: 1) To characterize the relationship between consumption of girl scout cookies and health risks; 2) To monitor changes in glucose and cholesterol levels after consuming the study agents for a period of up to 30 days; and 3) To determine how long it will take for glucose and cholesterol levels to return to baseline.
3.0 Animal Studies and Previous Human Studies Note other human or animal research on the topic and provide any references that are relevant to the design and conduct of the study.
4.0 Inclusion/Exclusion Criteria List the criteria: Bullet or number each criteria for easy identification Explain the procedures to determine eligibility Note any special assessments that will be conducted (e.g., depression or suicidal ideation screenings)
Inclusion/Exclusion Criteria Inclusion Criteria: Healthy volunteers Between the ages of 18-80 Exclusion Criteria: History of heart disease, uncontrolled diabetes Allergic reaction to peanuts or chocolate Inability or unwillingness to give informed consent
5.0 Enrollment/Randomization State how participants will be identified and recruited for the trial. Describe the procedure for consenting participants. Do potential participants have a relationship with the PI? If so, how will the PI remain impartial when presenting the study? How many participants will be consented and how many are anticipated to complete the trial?
5.0 Enrollment/Randomization Will any vulnerable populations be enrolled? How long will the study last? Does the study include blinding? Will participants receive a placebo? State the ratio for randomization (1:1- 2:1). Will the PI provide the pharmacy with a randomization schedule?
Enrollment/Randomization Participants will be selected from the… After expressing interest in the study, the coordinator will provide an overview of the study and obtain consent prior to initiating any research related procedures. Approximately xx participants will be consented with xx being expected to complete the study.
Enrollment/Randomization (cont) Participants will be randomized to receive either the active study agent or the placebo (1:1 ratio). Study agents will be provided by Girl Scouts of America and will be stored and dispensed through the Investigational Drug Service.
6.0 Study Procedures Will patients be withdrawn from current medications or other treatments? Is there a run-in period? Will participants have a baseline assessment for the status of the disease being studied? Are overnight stays involved? Who will administer the study drug?
6.0 Study Procedures Discuss doses and length of exposure to study drugs. Outline what will occur at each visit (labs, assessments, other tests). Consider including a chart or table. State measures that will be used to minimize risk and monitor participant safety.
Study Procedures Participants will be asked to come to the clinic, and upon arrival will have their blood drawn (10ml). Once the blood draw is complete the participant will be asked to consume the study agent. After a 30 minute rest period, a second blood draw (10ml) will be performed. The participant will be asked to consume a second study agent and will return to the waiting area. After another 25 minute rest period the participant will be asked to consume the final study agent and the blood draw (10ml) will be repeated. Patients will be monitored for signs or symptoms of an allergic reaction for an additional 60 minutes after the blood draw prior to being released.
Study Procedures Subjects will be discharged with a 30 day supply of the study agent and will be asked to consume 6 study agents per day. Weekly phone calls will be made to monitor for adherence and safety. A follow-up visit with a blood draw (10ml) will be conducted at the clinic between days 28-32. Participants will return any unused study agents at that time.
Study Procedures Three additional follow-up visits will be conducted at approximately 60, 90, and 120 days. Participants will be asked to provide a blood sample (10ml) at each visit to monitor glucose and cholesterol levels.
Study Procedures Participants will not be withdrawn from any current meds. The study agents will be administered by the study staff while at the study center and self-administered at home. Participants will be monitored for safety and compliance through weekly phone calls, which will be made by the study staff and will follow an approved script.
7.0 Risks State all adverse events observed in other previous animal or human studies or any laboratory observations. Note if there may be unknown risks Because this treatment is investigational, meaning non-FDA approved, there may be risks that we do not know about at this time.
Risks The active study agent contains peanut products. The risks associated with peanut allergies can range from a mild rash to an anaphylactic reaction. Other side effects: Weight gain Blood draw risks Rank according to common, uncommon and life-threatening/severe.
8.0 Reporting of Adverse Events or Unanticipated Problems What will be reported – be clear and specific. State the Data Safety Monitoring Plan. Is there a Data Safety Monitoring Board? If so, who are the members and how often will they meet? Provide reporting procedures to the sponsor, IRB, or federal agencies.
Reporting Adverse Events All anaphylactic reactions will be promptly reported to the IRB. The PI will be responsible for monitoring each participant during the study and for 60 minutes after the final ingestion of the study agent. Participants will be contacted on a weekly basis while receiving the study agents to monitor for adherence and adverse events.
9.0 Study Withdrawal/Discontinuation Explain the procedures for withdrawing a participant who decides to stop the study and the circumstances under which the PI would withdraw the participant (unacceptable adverse events, non- compliant, etc).
Study Withdrawal/Discontinuation Participants may withdraw from the study at any time. The study agent should not be stopped abruptly, but should be tapered instead. The PI will withdraw any participant who experiences an unacceptable adverse event or is non-compliant.
10.0 Statistical Considerations Provide evidence the study has adequate power to detect a difference between the two groups or to answer the question being asked. If the study could have multiple outcomes, has a power analysis been conducted for each outcome? Will an interim analysis be conducted to determine any difference between the study groups? Will predetermined rules be established for stopping the study due to futility?
Statistical Considerations Please consider using REDCap. Features include: Scheduling Building surveys Exporting data to Microsoft Excel, PDF, SIS, Stata, R, or SPSS for analysis Advanced features: auto-validation, calculated fields, file uploading, branching/skip logic and survey stop actions.
Statistical Consideration The primary endpoint is change from the baseline of blood glucose and cholesterol levels at 30, 60, 90 and 120 days.
11.0 Privacy/Confidentiality Issues How will the privacy and confidentiality of participants be protected? Will data be coded, stored in a password protected computer? Who has access to the code? Is information being shared with other Investigators or institutions?
Privacy/Confidentiality All study related materials will be maintained in a locked file cabinet or stored in a password protected, encrypted electronic database. Only the PI and study coordinator will have access to the cabinet key or password. Information will not be shared with other investigators or institutions.
12.0 Follow-up and Record Retention How long will patients be monitored or possibly screened for signs of disease? If there is evidence of disease, what procedures will be followed? How long will records be maintained after study completion? (Must be a minimum of 3 years)
Followup/Record Retention Participants will receive weekly follow-up phone calls and will return to the clinic for 4 follow-up visits. At each contact, participants will be asked if they have experience any adverse events. All study related documents will be retained by the Investigator for a minimum of 6 years. At this time, all records will be destroyed in accordance with HIPAA and institutional policies and procedures.
Criteria for IRB Approval (45 CFR 46) Risks to subjects are minimized Risks are reasonable in relation to anticipated benefits Selection of subjects is equitable Informed consent is obtained when required Informed consent is appropriately documented Data and safety monitoring is adequate Privacy and confidentiality are protected Additional safeguards are in place for vulnerable populations
References OHRP Determination Letter to John Hopkins is located at: http://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdfhttp://www.hhs.gov/ohrp/detrm_letrs/jul01a.pdf Schoenberg, 2006. The New Normal? What Girls Say About Healthy Living. http://www.girlscouts.org/research/publications/original/he althy_living.asp http://www.girlscouts.org/research/publications/original/he althy_living.asp IRB Policy VI.B, General Responsibilities of the Investigator FDA (Investigational Drugs) http://www.fda.gov/cder/info/healthcare.htm http://www.fda.gov/cder/info/healthcare.htm FDA (Investigational Devices) http://www.fda.gov/cdrh/ http://www.fda.gov/cdrh/