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Writing IRB application with this template 

DMID Interventional Protocol Template Version 2.0

28 April 2005

Protocol Title Version number and date

GENERAL INSTRUCTIONS – delete this box from the submitted Protocol

This template is for students in the Virginia University of Lynchburg Doctor of Healthcare Administration Research Practicum course who are preparing a detailed protocol for a study involving human subjects. Depending on the nature of what you are doing, some sections may not be applicable to your research. If a section is not applicable, delete. You may delete subsections that are not applicable. The full research protocol must be uploaded to Moodle to be considered complete. This includes the IRB Application with research protocol, Informed Consent Document (s), Recruitment Collateral, and any other supporting documentation. Applications with ANY missing elements will be considered incomplete and will be graded accordingly.

Use this template to create a study protocol as follows:

· Red text represents instructions to you – to be deleted from the final version

· Blue text represents guidance on suggested content – to be edited and changed to black or replaced with black in the final version.

· Black text represents text that should ordinarily be incorporated as-is, if applicable

Note that the table of contents is automatically included, so . Be sure to right click on the table of contents and select “Update field” before saving the protocol and uploading it to Moodle. As always, make sure to proofread the document before submission.

Please make sure to complete the header on this page with the protocol title and version number and date.

The submitted protocol should have no red or blue text (including the header and instruction boxes like this one). The submitted protocol should have no spelling or grammar errors. All references MUST be in APA 7 format.

PROTOCOL TITLE

Protocol Version Number: Complete

Protocol Version Date: day, month, year

[Include if there is an external funder; otherwise, delete heading] Funding Mechanism: organization and grant or contract #

[Include if there is industry support; otherwise, delete heading] Industry Support provided by: name of industry

Principal Investigator: name

Phone: Complete

E-mail: Complete

[Include if the study has a medical monitor; otherwise, delete heading] Medical Monitor: name


Table of Contents


1



List of Abbreviations






4




2



Protocol Summary






4




3



Background/Rationale & Purpose






5




3.1



Background Information






5




3.2



Rationale and Purpose






5




4



Objectives






5




4.1



Study Objectives






5




4.2



Study Outcome Measures






6




4.2.1



Primary Outcome Measures






6




4.2.2



Secondary Outcome Measures






6




5



Study Design






6




6



Potential Risks and Benefits






7




6.1



Risks






7




6.2



Potential Benefits






8




6.3



Analysis of Risks in Relation to Benefits






8




7



Study Subject Selection






8




7.1



Subject Inclusion Criteria






8




7.2



Subject Exclusion Criteria






8




7.3



Recruitment Methods






9




7.4



Compensation for Participation in Research Activities






9




7.5



Withdrawal of Participants






9




8



Study Intervention






9




9



Study Procedures






10




10



Assessment of Safety and Data Safety Monitoring Plan (DSMP)






10



10.1

Definitions





10



10.2

Safety Review





11




10.3



Reporting Plans






12



10.4

Stopping Rules





12




11



Data Handling and Record Keeping






12




11.1



Confidentiality






12



11.2

Source Documents





13




11.3



Case Report Forms






13




11.4



Study Records Retention






14




12



Statistical Plan






14




12.1



Study Hypotheses






14




12.2



Sample Size Determination






14




12.3



Statistical Methods






15




13



Ethics/Protection of Human Subjects






15




14



Literature References






15




15



Appendix






15



List of Abbreviations

[Complete this table with all disease or study-specific abbreviations/acronyms. Add rows as needed]

Abbreviation

Abbreviation definition



Protocol Summary

Limit to 1-2 pages

Title:

Study title.

Population:

Study population, sample size, sex, age, vulnerable populations if any.

Indicate

Special Population(s)

|_|Children

|_| Children who are wards of the state

|_| Adults Unable to Consent

|_| Cognitively Impaired Adults

|_| Neonates of Uncertain Viability

|_| Pregnant Women

|_| Prisoners (or other detained/paroled individuals)

|_| Students/Employees

Intervention:

For drugs: name, dose, route of administration, regimen (Drug/Device Handling: If the research involves drugs or devices, describe your plans to store, handle, and administer those drugs or devices so that they will be used only on participants and be used only by authorized investigators.); for other interventions: name, method, timing. (Provide a description of all research procedures being performed and when they are performed, including procedures being performed to monitor participants for safety or minimize risks.)

(Describe:

· Procedures performed to lessen the probability or magnitude of risks.

· Delineate which procedures are and which are . (For example, if the frequency of CT scans is within standard of care, this should be indicated)

· All drugs and devices used in the research and the purpose of their use, and their regulatory approval status.

· The source records, including medical or educational records that will be used to collect data about participants. (Attach all surveys, scripts, and data collection forms.)

Objectives:

Study objectives.

Design/Methodology:

Study arms, randomization, schedule of interventions and assessments. You may refer to a detailed schematic and/or table of visits and assessments in the Appendix.

Total Study Duration:

Time from when the study opens to enrollment until completion of data analysis

Subject Participation Duration:

Time it will take to conduct the study for each individual participant.





Background/Rationale & Purpose





Background Information

Include as appropriate:

· A brief description of the health condition or research question that the study will address

· The name and description of the study intervention/investigational product

· Discussion of important research and literature and current practice that provides background and scientific justification for the study and applicable clinical, epidemiological, or public health background or context of the study (ALL REFERENCES MUST BE IN APA 7 FORMAT)

· Known risks and potential benefits (briefly, these are addressed in detail later in the protocol)

· Importance of the study and any relevant treatment issues or controversies

· Any pertinent pre-clinical data and prior experience with intervention

[This statement is required] This study will be conducted in compliance with the protocol, applicable regulatory requirements, and Human Research Protection policies and procedures.





Rationale and Purpose

Describe why it makes sense to do this study and the importance/value of the information to be gained. Describe what is innovative or new and useful about the potential solutions including any new and enabling ideas or technologies, new approaches, unique resources developed or that will be accessed. Provide justification for the proposed use of the intervention in this manner and within the study population.






Objectives



Study Objectives

Provide a detailed description of the one primary objective and any secondary objectives of the study. An objective is the reason for performing the study in terms of the scientific question to be answered. The primary objective is the main question. This objective generally drives statistical planning for the research (e.g., calculation of the sample size to provide the appropriate power for statistical testing). Secondary objectives are goals that will provide further information on the use of the intervention.

Express each objective as a statement of purpose (e.g., to assess, to determine, to compare, to evaluate).





Study Outcome Measures




The sections below should include the methods for assessing how the objectives are met.

An outcome measure is a specific measurement or observation used to assess the effect of the study intervention. Outcome measures should be prioritized and should correspond to the study objectives and hypotheses being tested. Give succinct but precise definitions of the outcome measures used to address the study’s primary objective and key secondary objectives (e.g., specific laboratory tests that define safety or efficacy, clinical assessments of disease status, assessments of psychological characteristics, assessments of individual or group health behaviors, assessments of healthcare visit attendance, etc.). Include the study visits or time points at which data will be recorded or samples will be obtained.



Primary Outcome Measures

Generally, there should be just one primary outcome measure that will provide a clinically relevant, valid, and reliable measure of the primary objective.



Secondary Outcome Measures

List additional outcome measures.





Study Design






The scientific integrity of the research and the credibility of the data derived from the research depend substantially on the research design. This section should include, as applicable (but not be limited to):

A brief description of the type/design of research to be conducted (e.g., randomized, placebo-controlled, masking, parallel group, matching, cross-over, open-label, dose-escalation, dose-ranging)

A description of the randomization process if applicable

A description of the study population (e.g., healthy/sick, inpatient/outpatient, demographic groups). Do not list detailed inclusion/exclusion criteria here, as these will be listed in later sections.

A brief discussion of the rationale for design features

Phase of trial, if applicable

The number of study groups/arms and descriptions

Planned variation in intervention, dose, or schedule (e.g., dose escalation)

A brief summary of methods for collecting data for assessment of study objectives

Audio/Video Recording/Photography: If applicable, describe:

· the type of recording/photography being utilized

· why the type of recording is necessary to the research

· how the recordings/photograph(s) will be utilized in the research (e.g., data analysis only)

· how and where the recordings/photograph(s) are stored, who has access to them, and if/when they will be destroyed.)

Other protocol-specific details, such as centralization of evaluations (e.g., central laboratory or central reading center for clinical scans)

[Include if a schematic of the study design is in the Appendix; otherwise, delete sentence] See the Appendix for a schematic of the study design.



Potential Risks and Benefits



Risks

Describe in detail any reasonably foreseeable physical, psychological, social, legal, economic, or any other anticipated risks to study subjects. Include risks of study intervention and other study procedures. Describe procedures to minimize risks.

If applicable, indicate:

· which procedures may have risks to the participants that are currently unforeseeable.

· which procedures may have risks to an embryo or fetus should the participant be or become pregnant.

· risks to others who are not participants.)

One or more of the following may serve as the source of risk information:

Package insert for a licensed product

Investigator’s Brochure (IB) for an investigational product

Preclinical data reports

Literature search and review (cite references and list them in Section 14)


Provisions to Monitor the Data to Ensure the Safety of Participants

(This section is required when research involves more than Minimal Risk to participants.)

Describe:

· The plan to periodically evaluate the data collected regarding both harms and benefits to determine whether participants remain safe. The plan might include establishing a data monitoring committee (DSMB/DMC/IDMC) and a plan for reporting data monitoring committee findings to the IRB and the sponsor.

· The frequency of DSMB Meeting.

· What data are reviewed, including safety data, untoward events, and efficacy data.

· How the safety information will be collected (e.g., with case report forms, at study visits, by telephone calls with participants).

· The frequency of data collection, including when safety data collection starts.

· Who will review the data.

· The frequency or periodicity of review of cumulative data.

· The statistical tests for analyzing the safety data to determine whether harm is occurring.

· Any conditions that trigger an immediate suspension of the research.)

Compensation for Research-Related Injury

(If the research involves more than Minimal Risk to participants, describe the available compensation in the event of research-related injury.)

· (Provide a copy of contract language, if any, relevant to compensation for research-related injury.)



Potential Benefits

If the research is beneficial, describe any physical, psychological, social, legal, or any other anticipated benefits to subjects. While it may not provide direct benefit to subjects, the importance of the knowledge that may result from the study may be mentioned. Note: Compensation to subjects is not considered a “benefit.”



Analysis of Risks in Relation to Benefits

Describe how risks to subjects are reasonable in relation to anticipated benefits, if any, to subjects, and the importance of the knowledge that may reasonably be expected to result.



Study Subject Selection





Subject Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

· Inclusion criteria

· Describe:

· how individuals will be screened for eligibility,

· the criteria that define who will be included or excluded in your final study sample,

· specify if you will include or exclude each of the following special populations (members of the populations below may not be included in your research unless you indicate this in your inclusion criteria):

· Adults unable to consent

· Individuals who are not yet adults (infants, children, teenagers)

· Pregnant women

· Prisoners

· Vulnerable Populations

If the research involves individuals who are vulnerable to coercion or undue influence, describe additional safeguards included to protect their rights and welfare.

If the research involves non-English speaking participants indicate what language(s) other than English are understood by prospective participants or representatives. If participants who do not speak English will be enrolled, describe the process to ensure that the oral and written information provided to those participants will be in that language. Indicate the language that will be used by those obtaining consent.





Subject Exclusion Criteria

An individual who meets any of the following criteria will be excluded from participation in this study:

· Exclusion criteria; do not duplicate what is already listed in the Inclusion criteria above; if no additional criteria, say “None.”

· If this study excludes certain populations, explain the rationale for the exclusion in detail.



Recruitment Methods

Describe when, where, and how potential participants will be recruited including the source of participants and any methods that will be used to identify potential participants.

Describe materials that will be used to recruit participants. (Attach copies of these documents in the appendix of the application. For advertisements, attach the final copy of printed advertisements.

When advertisements are taped for broadcast, attach the final audio/video file. You may submit the wording of the advertisement prior to taping to preclude re-taping because of inappropriate wording, provided the IRB reviews the final audio/video file.



Compensation for Participation in Research Activities

Describe the amount, timing, and method of any payments to participants. (e.g., gift card, meals, check.)

If payment is by check, you must request name, address and Social Security Number in order to issue a check for participation. Study payments are considered taxable income and are reportable to the IRS.

If the investigator believes that the biologic specimens obtained could be part of or lead to the development of a commercial product, indicate if the participant will have any right to compensation or ownership interest related to such development.

Describe when and how participants will be informed of the results of the research.



Withdrawal of Participants

Describe:

· any anticipated circumstances under which participants will be withdrawn from the research without their consent,

· any procedures for orderly termination,

· procedures that will be followed when participants withdraw from the research, including partial withdrawal from procedures with continued data collection.









Study Intervention







The study intervention may involve an investigational drug or device, an approved drug or device, a behavioral intervention, and/or a surgical or other intervention. Provide a detailed description of the intervention, including any placebo or other control interventions.

If the study is testing drug/biologic(s) include the following:

How the study product will be acquired

The formulation, packaging, and labeling of the product as supplied

Product distribution, storage and stability

Dosage, preparation, and administration

Instructions for modification of dose due to toxicity or other reason.

Accountability procedures and compliance assessment



Study Procedures

[Include; a schedule of events that lists all visits/contacts and procedures at each visit/contact must be included in the Appendix] See the Appendix for the schedule of events.

Include a description of all study visits and all other contacts, such as telephone and/or email/text contacts. Include visit windows, considering feasibility and relevance of the time point to study outcome measures (e.g., pharmacokinetic studies may allow little or no variation, with required time points measured in minutes or hours, whereas a 6-month follow-up visit might have a window of several weeks).

Describe evaluations/procedures necessary to assess or confirm whether a subject will meet eligibility criteria and may be enrolled. Describe in detail all tests and procedures at follow-up visits. Include a table that lists visits and procedures at each visit. Describe the final study visit as well as an early termination visit, as necessary.

Include the total study duration (anticipated time between the beginning of study activities to the completion of data analysis) and the subject participation duration (the time between enrollment and the end of study activities for an individual subject).

Describe all clinical and laboratory evaluations. Make sure to clarify as needed which procedures would happen anyway, if the subject were not in the research, and which procedures are happening due to the research. Any special handling, processing, or shipping of laboratory specimens should be described, including long-term storage for research purposes.

As appropriate, describe intervention-assignment procedures, randomization procedures, and reasons subjects may be withdrawn from the study without their consent. Describe any procedures necessary in the case of early termination or withdrawal of subjects.

If the study is blinded, describe procedures for masking procedures, maintaining the blinding and procedures for unblinding study intervention for a particular subject due to safety reasons.





Assessment of Safety and Data Safety Monitoring Plan (DSMP)



Definitions

[Edit if necessary to make these definitions specific to the study. Non-medical studies will require editing of the definition of Adverse Event. If a Medical Campus PI is also the FDA sponsor FDA definitions should be used. Include any specific provisions for pregnancy in female subjects and/or in female partners of male subjects.]

The following definitions will be used in the assessment of safety:

Adverse Event (AE)
is any untoward or unfavorable medical occurrence in a human subject, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the subject’s participation in the research, whether or not considered related to the subject’s participation in the research.

Serious Adverse Event (SAE) is any adverse event that

(1) results in death;

(2) is life-threatening;

(3) results in inpatient hospitalization or prolongation of existing hospitalization;

(4) results in a persistent or significant disability/incapacity;

(5) results in a congenital anomaly/birth defect; or

(6) based upon appropriate medical judgment, may jeopardize the subject’s health and may require medical or surgical intervention to prevent one of the other outcomes listed in this definition (examples of such events include allergic bronchospasm requiring intensive treatment in the emergency room or at home, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse).

Life-threatening means that the event places the subject at immediate risk of death from the event as it occurred.

Unanticipated Problem
is defined as an event, experience or outcome that meets all three of the following criteria:

· ; AND

· to participation in the research; AND

· suggests that the research of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

Possibly related means there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research

Unexpected means the nature, severity, or frequency of the event is not consistent with either:

· the known or foreseeable risk of adverse events associated with the procedures involved in the research that are described in (a) the protocol–related documents, such as the IRB-approved research protocol, any applicable investigator brochure, and the current IRB-approved informed consent document, and (b) other relevant sources of information, such as product labeling and package inserts; or

· the expected natural progression of any underlying disease, disorder, or condition of the subject(s) experiencing the adverse event and the subject’s predisposing risk factor profile for the adverse event.


Safety Review

Both the risks listed in Section 4.1 and unknown risks will be monitored as follows: a description of what risks will be monitored, by whom, and how often; how Adverse Events will be evaluated for severity, seriousness, relatedness, and expectedness; how events that are not Adverse Events will be assessed for expectedness, relatedness, and suggesting new risks; when and how aggregate Adverse Events will be evaluated to determine whether there are trends that could affect subject safety; and when and how the blind may be broken to assess events/outcomes by study arm. If there is an independent monitoring committee (such as a Data Safety Monitoring Board), you MUST also include a charter document as an appendix that describes the purposes and specific functions and processes of the safety monitoring entity.




Reporting Plans

The Principal Investigator will report Unanticipated Problems, safety monitors’ reports, and Adverse Events to the IRB in accordance with IRB policies:

· Unanticipated Problems involving a fatal or life-threatening event will be reported to the IRB within 2 days of the investigator learning of the event.

· Unanticipated Problems not involving a fatal or life-threatening event will be reported to the IRB within 7 days of the investigator learning of the event.

· Reports from safety monitors with recommended changes will be reported to the IRB within 7 days of the investigator receiving the report.

· Adverse Events (including Serious Adverse Events) will be reported in summary at the time of continuing review, along with a statement that the pattern of adverse events, in total, does not suggest that the research places subjects or others at a greater risk of harm than was previously known.

· Reports from safety monitors with no recommended changes will be reported to the IRB at the time of continuing review.

[Include if there is one or more safety monitoring entity; otherwise, delete paragraph] The Principal Investigator will report Unanticipated Problems and Adverse Events to name of entity; schedule of reporting requirements

[Include if there is one or more safety monitoring entity; otherwise, delete paragraph] Name of entity will communicate its reports and recommendations as follows: schedule of reporting by the safety monitoring entity to the PI, IRB, and/or sponsor.



Stopping Rules

[Include if the study has no stopping rules; otherwise, omit sentence] The study has no stopping rules.

[Include if the study does have stopping rules; otherwise, omit paragraphs] A subject will be withdrawn from the study if adverse event(s) requiring subject withdrawal.

The study will be stopped if rules for stopping for safety, futility, etc.





Data Handling and Record Keeping



Confidentiality

Include

· procedures for maintaining subject confidentiality for data and/or biospecimens (e.g., training, authorization of access, password protection, encryption, physical controls, certificates of confidentiality, and separation of identifiers and data) during storage, use, and transmission.

· any special data security requirements

· If data or specimens will be stored, describe

· where the specimens will be stored,

· how long they will be stored,

· how the specimens will be accessed,

· who will have access to the specimens, and

· the data to be stored or associated with each specimen

· any plans for sharing data and/or biospecimens, identified or de-identified

· Describe the procedures to release data or specimens, including: the process to request a release, approvals required for release, who can obtain data or specimens, and the data to be provided with specimens.

· any plans for registering and updating on ClinicalTrials.gov.

[Include if the study has an external sponsor, modified as applicable; otherwise, delete] The study monitor or other authorized representatives of the sponsor may inspect all documents and records required to be maintained by the investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy records for the subjects in this study. The clinical study site will permit access to such records.


Source Documents

Describe source data and source documents. Source data is all information, original records of findings, observations, or other activities in research necessary for the reconstruction and evaluation of the research. Source data are contained in source documents. Examples of these original documents, and data records include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated instruments, copies or transcriptions certified after verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at medico-technical departments involved in the research.

Procedures should ensure that source data meet the “ALCOA” standards: Attributable, Legible, Contemporaneous, Original, and Accurate.

[Include and modify as applicable] Data generated by the methods described in the protocol will be recorded in the subjects’ medical records and/or study progress notes. Data may be transcribed legibly on CRFs supplied for each subject or directly inputted into an electronic system or any combination thereof.



Case Report Forms

[Include and modify as applicable] The study case report form (CRF) will be the primary data collection instrument for the study. All data requested on the CRF will be recorded. All missing data will be explained. If a space on the CRF is left blank because the procedure was not done or the question was not asked, “N/D” will be written. If the item is not applicable to the individual case, “N/A” will be written. All entries will be printed legibly in black ink. If any entry error has been made, to correct such an error, a single straight line will be drawn through the incorrect entry and the correct data will be entered above it. All such changes will be initialed and dated. There will be no erasures or white-out on CRFs. For clarification of illegible or uncertain entries, the clarification will be printed above the item, then initialed and dated. [Include if any source data will be recorded directly on the CRF; otherwise, omit sentence] The following source data will be recorded directly on the CRFs: data where the CRF will be the source document.

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