Z:Resprot.Prn.Pdf

Guidelines for Writing a Research Protocol

NOTE: This template is to be used as a guide for prospective studies that would not meet the exempt criteria for the UW IRB.

The format and information provided below is suggested when writing a new research protocol. Not all sections will be relevant to all studies, but by writing a complete protocol you will provide the Emergency Medicine Research Committee members with all of the information they need when reviewing the study, will be able to more easily complete the on-line ARROW submission, and will more easily complete the pre-IRB scientific review.

Study Title

Principal Investigator – Name and Address

1. TITLE PAGE 1.1 Includes PI, Co I, Key personnel, Sponsor/Funder and participating sites 1.2 Table of Contents

2. PURPOSE OF THE STUDY AND BACKGROUND

2.1. Abstract Summarize the issue(s) to be addressed by the study. Include background, target population, anticipated outcomes.

2.2. Purpose of the study & Aims State the specific scientific primary objective (aim) of the research, as well as any secondary objectives. All objectives should be scientifically sound and achievable. Exploratory studies undertaken early in the development of a drug/device may have many objectives, whereas in confirmatory studies, they may be limited. Indicate secondary or other objectives as applicable.

2.3. Background In order to understand the rationale for the study, provide sufficient background information on: relevant prior knowledge or preliminary data; gaps in current knowledge; the development of the drug/device, its potential role in the disease process being studied, and relationship to current medical treatment; a summary of epidemiological data; and the significance of the research and how it will add to existing knowledge. Include any references with citations from literature.

3. STUDY DESIGN

3.1. Overview A brief overview of the study design intended to indicate how the objective(s) will be achieved. Comment on the type of study, i.e., single center or multicenter, double-blind (DB), randomized, crossover or parallel group, the type of control (placebo, active), specific treatment groups, method of subject assignment, and the sequence and duration of the study periods. 3.2. Rationale for Study Design and Measures Provide reasons why this study design was chosen. Explain how critical decisions on study design were derived and describe any atypical features of the design. Include known or potential problems with the design. Include discussion of the hypothesis and study objectives and why specific primary/secondary variables were chosen. Also, include measures to be used for each proposed outcome variable (using a table is recommended). Include any references with citations from literature.

3.3. Rationale for Intervention Include detailed description of intervention to be studied and rationale for the evaluation.

4. CHARACTERISTICS OF THE RESEARCH POPULATION

4.1. Subject Characteristics

1.a) Number of Subjects: State the total number of subjects expected to participate. This includes the number of evaluable subjects (i.e., those who meet eligibility criteria), as well as the number of anticipated screen failures necessary to obtain the enrollment goal (i.e., subjects consented but did not continue in the study as an evaluable subject). A subject is considered in the total count once informed consent has been obtained. If evaluable subjects who withdraw from the study will be replaced to meet the enrollment goal, this should also be stated here. In the case of multi-site coordinating center protocols, be sure to include all enrolling sites in the overall total.

1.b) Gender and Age of Subjects: Describe the intended gender distribution and age range of the subjects. Provide justification for any gender based enrollment restrictions and provide rationale for the selected age range. Equitable inclusion of both men and women in research is important to ensure that both receive an equal share of the potential benefits of research and that neither bears a disproportionate burden. Therefore, subjects of both genders should be included in the study unless there are appropriate medical and/or scientific reasons. Participation of adult subjects in research should not be age-restricted unless there is scientific reason.

1.c) Racial and Ethnic Origin: Describe the intended racial and ethnic distribution of the subjects. Provide justification for any enrollment restrictions based upon race or ethnic origin.

1.d) Vulnerable Subjects: Remove section if not applicable] If subjects who are vulnerable to coercion or undue influence will be enrolled (including children, pregnant women, the elderly, students, employees such as residents , fetuses, prisoners and persons with decisional impairments) provide justification for their inclusion in the study and a description of any additional safeguards that will be applied to protect their rights and welfare.

4.2. Inclusion and Exclusion Criteria

2.a) Inclusion Criteria: List (in bullets or in a table) the criteria that each subject must satisfy to be eligible for study participation. Define the eligible subject population in terms of age, sex, race, language, domicile, ability to give informed consent, diagnosis requirements, treatment requirements and ability to perform study- related functions.

2.b) Exclusion Criteria: List (in bullets or in a table) the criteria that will prevent inclusion of an inappropriate subject into the trial. Consider any condition that would prevent a subject from successfully participating in study required activities.

4.3. Discussion of Subject Population Present a brief discussion of why the inclusion/exclusion criteria were selected (e.g., the criteria are designed for a specific disease entity and population) in order to minimize the risks and account for the subject’s safety.

5. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT

5.1. Method Of Subject Identification And Recruitment How will subjects be identified and selected for the study? How will privacy of the individuals be maintained?

The identification and recruitment of subjects must protect privacy and be free of undue influence. Only investigators with routine access to prospective subjects (or subject records) may recruit those individuals directly (“routine access” meaning the investigator already has a clinical/academic reason to know/review a patient’s record or is known to the prospective subject). Investigators who do not have routine access to prospective subjects may not contact subjects directly (i.e., no “cold calls”); they must work through the individual(s) with routine access. Private information includes information about behavior that occurs in a context in which an individual can reasonably expect that no observation or recording is taking place, and information which has been provided for specific purposes by an individual and which the individual can reasonably expect will not be made public (for example, a medical record). 5.2. Process of Consent Describe who will obtain consent and how the process of informed consent will be structured. Only individuals who have completed the IRB’s required human subjects training and are listed on the IRB application are authorized to obtain consent. The process should be free of coercion and undue influence, and should provide enough information and sufficient time to be conducive to rational and thoughtful decision making by the subject/subject's authorized representative

All investigators have a legal and ethical obligation to ensure that any prospective subject has sufficient knowledge and comprehension of the elements of informed consent to enable them to make an informed decision whether or not to participate (or allow participation in research if authorized representative is delegated – see paragraph below). Describe how it will be determined that the subject understood the information presented. This section should clearly document that the investigator has an adequate plan in place to assure an acceptable level of comprehension before consent is obtained. If subjects will be capable of providing initial consent to enroll, but will possibly or probably lose that capacity as the study progresses, provide provisions for the subject to designate an authorized representative (see also paragraph below).

When the inclusion of vulnerable populations, such as children, the elderly, pregnant woman, prisoners or subjects with diminished capacity are proposed for the research this section should also include a specific plan to assess comprehension during consent or assent (the subject’s agreement). If subjects will not have the capacity to give informed consent, describe how capacity will be assessed and documented, how subjects will be informed of the decision to seek permission from an authorized representative, and whether assent from the subject will be solicited. Describe the anticipated degree of impairment relative to their ability to consent to participate in research.

Describe how consent will be documented and how/where documentation will be stored. If applicable, describe under what conditions a witness or translator will be used. If a waiver of consent or a waiver of documentation of consent is requested for part of the study (or its entirety), describe here and provide justification.

6. METHODS AND STUDY PROCEDURES In this section provide the full study procedures in detail. Consider this a step-by-step detail of what you will do in the research study.

If the study is a randomized controlled trial (RCT) describe each group and what the differences between the conditions. Outline the assessments that will be performed. In addition, include the treatment plan if applicable. Procedures/tests/interventions which are considered experimental and/or procedures performed exclusively for research purposes must be identified and differentiated from that which would occur regardless of the research (i.e., standard of care).

Provide a schedule of study visits and identify what study procedures will be conducted at each visit to accomplish the objectives of the study (a chart or table indicating the visit schedule and the activities to be conducted at each visit may be inserted here, or as an appendix to the protocol – see sample Appendix 1). If applicable, unscheduled visits, telephone visits, end of study visits and early withdrawal visits should be included in this description.

6.1. Efficacy Assessments Describe the assessments that will be performed to evaluate efficacy. The description should clearly state who is responsible for performing the assessment (e.g., Investigator, Coordinator, Subject, etc.). If the subject is asked to describe symptoms, specify the rating scales to be used by the subject to quantify symptoms and signs, how the subject is to be trained to make and record these assessments and how subject compliance is to be checked. Describe any special precautions that need to be taken. Describe any special procedures in detail that will be performed, (e.g., CT scans).

6.2. Safety Assessments Describe the assessments that will be performed to evaluate safety (e.g., medical history, physical exam, vital signs, clinical labs). Describe any special procedures in detail that will be performed, (e.g., ECGs).

6.3. Assessment of Subject Compliance If the Investigator or Coordinator will assess the subject’s compliance with the protocol, concomitant medication use, diaries, or use of study drug, those procedures should be described here.

6.4. Data & Specimen Banking for Future Research Use [Remove section if not applicable] Indicate whether data and/or specimens will be banked for future research use. If so, describe the purpose for storing the data/specimens, including the type of research that will be conducted with the data/specimens; where the data/specimens will be stored; who will have access to the data/specimens and the conditions (if any) under which they will be released to investigators outside the study team; how long the data/specimens will be stored and whether they will be destroyed at any time point; procedures for maintaining confidentiality of subjects (i.e. will the data/samples be coded to allow subjects to be identified); whether subjects may withdraw the sample and/or data and the process for doing so if applicable; and whether or not subjects would be re-contacted regarding the banked data/specimens.

6.5. Costs to the Subject Normally, subjects should not have to pay for research procedures. Describe and justify any costs (i.e., study procedure/drug/device and/or standard of care) that the subject or the subject’s insurance will or may incur as a result of participating in the study. Indicate who will pay for procedures associated with the study (e.g., agency grant versus departmental funds). No charge may be made to subjects if the study costs are already covered by a grant, contract, or other payment method.

6.6. Payment for Participation Describe any reimbursements or payments (e.g., cash payments, coupons) that the subjects will receive for participation. List the prerequisite condition(s) that must be fulfilled by subjects to receive these payments. The amount must be justified and not constitute undue inducement of the subject to participate in the research or to continue beyond a point that they would have otherwise withdrawn. 6.7. Return of Individual Research Results Describe whether research results will be provided back to the subject (e.g., lab results, psychological or neurological assessment results, genetic test results), and if so, when they will be provided (e.g., not until the study is completed, at the time the Investigator receives the result, etc.). As appropriate, describe how incidental findings that might have health consequences for the individual subject will be managed.

7. SUBJECT WITHDRAWALS Subjects will be advised in the written informed consent forms that they have the right to withdraw from the study at any time without prejudice. If subjects may be withdrawn by the investigator/sponsor, describe anticipated circumstances under which subjects will be withdrawn from the research without their consent (e.g., non-compliance, worsening of the disease under study, pregnancy, homelessness, termination of funding,). Describe whether additional study activities will be completed prior to subject withdrawal from the study. Indicate whether subjects withdrawn from the study will be replaced.

8. SAFETY AND REPORTABLE EVENTS Use the NIH definitions of Adverse Events (AE), Severe Adverse Events (SAE) and Unanticipated Problems (UP) in your protocol. The NIH definitions are as follows: 8.1. Adverse Event Definition ● Any untoward or unfavorable medical occurrence in a human study participant, including any abnormal sign (e.g. abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participants’ involvement in the research, whether or not considered related to participation in the research. 8.2. Serious Adverse Event Any adverse event that: ● Results in death ● Is life threatening, or places the participant at immediate risk of death from the event as it occurred ● Requires or prolongs hospitalization ● Causes persistent or significant disability or incapacity ● Results in congenital anomalies or birth defects ● Is another condition which investigators judge to represent significant hazards

8.3. Unanticipated Problem (UP) This is any incident, experience, or outcome that: ● Is unexpected, in terms of nature, severity, or frequency, given (a) the research procedures and (b) the characteristics of the study population; ● Is related or possibly related to participation in the research (i.e., reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research); ● Suggests that the research places participants or others at a greater risk of harm (including physical, psychological, economic, or social harm) than was previously known or recognized.

8.4. Recording Adverse Events All adverse events, whether observed by the Investigator, elicited from or volunteered by the subject, should be documented. Each adverse event will include a brief description of the experience, the date of onset, the date of resolution, the duration and type of experience, the severity, the relationship to the study, contributing factors, and any action taken.

Also, indicate the timeframe that recording of adverse events will occur (e.g. once the subject signs consent until subject completes the study or withdraws from participation). Indicate the requirements for follow up of adverse experiences (e.g., until event is resolved or stabilized), including those that are ongoing/unresolved at the time of subject concluding study participation.

8.5. Responsibilities for Reporting Serious Adverse Events The Investigator should record all serious adverse experiences that occur during the study period in the appropriate source documents and/or AE log as applicable. The study period for reporting serious adverse events (e.g., from the time of signing consent to final study visit) should be indicated, who needs to be notified and the time frame for notification. If there are any specific reporting forms to be completed, this should be indicated here. The Investigator will comply with regulations and IRB policy regarding the reporting of adverse events.

9. RISK/BENEFIT ASSESSMENT

9.1. Potential Risks Describe the potential risks associated with the study (including potential risks to individuals other than the subject). Risks are not only physical, but psychological, sociological, economic and legal as well. This includes any specific toxicity data noted in the investigator’s brochure/package insert. If possible, estimate the probability that a given harm may occur and state its potential reversibility.

9.2. Protection Against Risks Describe how the study design will prevent and/or minimize any potential risks or discomfort. Potential risks and discomforts must be minimized to the greatest extent possible by using procedures such as appropriate training of personnel, monitoring, withdrawal of the subject upon evidence of difficulty or adverse event; and referral for treatment, counseling or other necessary follow-up. State who will pay for treatment, counseling or follow-up.

9.3. Potential Benefits to Subjects Describe potential direct benefit(s), if any, for subjects participating in the research. If there are no anticipated benefits, this should be stated. Do not include subject payments or benefits to society or others.

9.4. Alternatives to Participation Provide a description of alternative courses of action which are available should the subject elect not to participate in the study. If there are no alternatives available to the subject, this should be stated. 10. CONFIDENTIALIATY OF DATA AND INFORMATION STORAGE Confidentiality is the ethical and/or legal right that information, such as research data, will be held secret and safeguarded from disclosure unless consent is provided permitting disclosure. Indicate how subject data will be identified in the research data set (e.g., random sequential numbering or unique identifiable code). If research specimens are used, indicate how the samples will be labeled (e.g., the same subject ID number, barcode, etc.). If any individual subject identifiers are collected, explain how you will protect against disclosure of those identifiers. A random unique code is permitted and is not considered an individual identifier if the code is not derived from or related to the information about the individual, could not be translated to identify the individual, and the key is securely retained. If a random unique code will be received (i.e., a code not derived from or related to the information about the individual) that could be used for purposes of re-identification, explain who maintains the link or key to that code and whether it will be used for re-identification or destroyed. If internet based research is planned within the protocol, the level of encryption used by the online survey tool must be described as a protection against the risks of loss of confidentiality.

Describe where the research data will be stored during the study and how it will be secured. This includes coding data and choosing an appropriate and secure data storage mechanism which will prevent unauthorized access to data. State who will have access to the data. If data with subject identifiers will be released, specify the person(s) or agency to whom the information will be released and the purpose of the release (e.g., routine verification of case report forms).

Examples for maintaining confidentiality of data and protecting against unauthorized disclosure may include: ● not storing identifying information in the research database except subject ID number (i.e., keep any identifying information separately from the research database) ● using a random unique code assigned to each subject (see definition of random unique code above) ● locking up research files while they are unsupervised ● using screensavers ● encryption of the data ● shredding excess copies of paper documents ● protections for codes that link patients to their data ● electronic and physical security of data storage devices and networks ● security measures to protect storage and transmission of electronic data.

11. RESEARCH INFORMATION IN MEDICAL RECORDS Indicate if any research data will be included in the subject’s medical record (e.g., lab test results, drug assignment, or indication of study participation)

12. DATA ANALYSIS AND MONITORING 12.1. Sample Size Determination Provide the planned sample size and the basis for it, i.e., statistical considerations and/or practical limitations. Provide the formula for sample size and power calculations together with a reference source, if necessary. State assumptions used in the calculations, e.g., variance, size of effect to be detected, Type I and Type II error probabilities, and provide explanations as to how they were obtained, where appropriate.

12.2. Planned Statistical Analysis Summarize the statistical/analytical methods to be used. Describe primary endpoints that will be analyzed, as well as any secondary endpoints as applicable.

12.3. Data and Safety Monitoring See the IRB Data and Safety Monitoring Plan policy for more information regarding data monitoring requirements. A data and safety monitoring plan must be established appropriate to the nature, size, and complexity of the protocol to assure that an adequate process is in place for oversight and monitoring of the conduct and progress of the study (for example, a Data and Safety Monitoring committee) to ensure: 1) important information that may affect the safety or welfare of subjects is noted and addressed as quickly as possible, and 2) the validity and integrity of the data. The plan should provide a detailed description of the operations of the committee or board (i.e., membership, function, frequency of review, stopping rules).

13. REFERENCES Provide complete, numbered references for all citations listed in the order that they appear.