Guidelines for Writing a Research Protocol – Biomedical

(RSRB Protocol Template Finalv. 11/07/2014)

The format and information provided below is suggested when writing a protocol that includes investigational drugs or devices.

Study Title

Principal Investigator – Name and Address

  1. PURPOSE OF THE STUDY AND BACKGROUND

1.1.Purpose of the study

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.

1.2.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.

  1. STUDY DESIGN

2.1.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.

NOTE: Investigators conducting research in foreign countries should refer to the Guideline for Conducting International Researchto ensure that items are addressed and additional protocol elements are considered and adequately described.

2.2.Rationale for Study Design

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.Include any references with citations from literature.

2.3.Rationale for Dosage

Describe the study drug route of administration and dosage with supporting evidence for why it was chosen, (e.g., [DRUG NAME] is being given IV over 30 minutes based on volunteer studies in elderly subjects in which it was well tolerated). Address the necessity for specified lengths of run-in, treatment, and post-treatment follow-up periods, if appropriate.Include any references with citations from literature.

  1. CHARACTERISTICS OF THE RESEARCH POPULATION

3.1.Subject Characteristics

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 centerprotocols,be sure to include all enrolling sites in the overall total.

NOTE: If enrollment will exceed the number for which your study is approved, an amendment must be submitted and RSRB approval of this amendment obtained before exceeding that number.

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 and/or medical justification.

NOTE: The age of majority in New York State is 18. Special considerations apply to research with children.

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.

NOTE: Within the limitations imposed by the population of the study site(s) and the purpose of the study, research should include sufficient enrollment of persons of diverse racial/ethnic backgrounds to ensure that the benefits and burdens of research participation are distributed in an equitable manner.]

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, 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.

3.2.Inclusion and Exclusion Criteria

NOTE: Enrolling a person who does not fit eligibility criteria listed here is a protocol violation and may require notification to RSRB as a reportable event.

a)Inclusion Criteria: List (in bullets) the criteria that each subject must satisfy to enter the study. Define the eligible subject population in terms of age, sex, race (as appropriate), diagnosis requirements, method of diagnosis, treatment requirements, ability to perform study-related functions, and the ability to give informed consent.

b)Exclusion Criteria:List (in bullets) the criteria that will prevent inclusion of an inappropriate subject into the trial. Consider previous and current disease, existing or previous therapy, disease severity, pregnancy and fertility, participation in other investigational drug studies, and a time frame for entry after discontinuing disallowed medications.

NOTE: Women of childbearing potential may not be routinely excluded from participating.

3.3.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.

  1. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT

4.1.Method Of Subject Identification And Recruitment

How will subjects be identifiedand 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).

NOTE: Recruitment of an investigator’s own students, employees or patients is considered potentially coercive. Steps taken to minimize undue influence should be included in the study protocol.

4.2.Process of Consent

Describe who will obtain consent and how the process of informed consent will be structured. Only individuals who are listed on the RSRB application (page 1 and Sect. 85.1) and RSRB approved 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).

[Remove section if not applicable] When the inclusion of vulnerable populations, such as children, pregnant woman, prisoners or subjects with diminished capacity are proposed for the research (see RSRB policy regarding research involving vulnerable populations), 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 documentedand 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.

  1. METHODS AND STUDY PROCEDURES

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.

Outline below the assessments that will be performed to evaluate efficacy and those to evaluate safety. 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).

5.1.Treatment Dosage and Administration

5.1.1.For studies with multiple treatment phases or arms, provide a summary of the entire treatment plan. Details will be described below.

5.1.2.Provide a full description of the treatment(s) and how it will be administered (i.e., inpatient or outpatient). A chart or table indicating the planned treatment regimen may be used (see example below). Also include a description of any required or recommended/suggested supportive care medications, as applicable. For orally administered agents, a method for assessing compliance with study drug should be included (e.g., use of a diary). Applicable dose modifications would be described under Section 8.

REGIMEN DESCRIPTION
Agent / Premedications;
Precautions / Dose / Route / Schedule / Cycle Length
Agent X / Premedicate with DRUG for 3 days prior to Agent X. / 300 mg/m2 in
500 cc NS / IV over 2 hours before Agent Y / Days 1-3, week 1 / 4 weeks (28 days)
Agent Y / Avoid exposure to cold (food, liquids, air) for 24 hrs after each dose. / 150 mg/m2 in
250 cc D5W / IV 1 hr after completion of Agent Y; separate IV line required / Days 1-3, week 1
Agent Z / Take with food. / 50 mg tablet / PO in the a.m. / Daily, wks 1 & 2

5.1.3.IND Agent(s)

Please describe in detail any prophylactic or supportive care regimens required for investigational study agent(s) administration and state any special precautions or relevant warnings (e.g., incompatibility of agent with commonly used intravenous solutions, necessity of administering agent(s) with food, premedications, etc.).

5.1.4.Other Agent(s)

Please describe in detail any prophylactic or supportive care regimens required for administration of each other agent in the treatment andstate any special precautions or relevant warnings (e.g., incompatibility of agent with commonly used intravenous solutions, necessity of administering agent with food, premedications, etc.).

5.2.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).

5.3.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).

5.4.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.

5.5.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.

5.6.Genetic/Genomic Research Activities

[Remove section if not applicable] If genetic and/or genomic research activities are proposed as either the main objective of the study, or as an ancillary activity within the protocol, the following information should be described here: a general description of the test and the purpose for conducting the test; whether professional genetic counseling will be provided to the subject before and/or after consent is obtained; a description of the specific disease(s) or condition(s) that are being tested for; name of individual(s) or organization(s) to test results may be disclosed; whether test results will be provided to the subject and explanation as to why they will/will not be provided; explanation for the meaning of a positive test result for the disease/condition being studied and level of certainty that the result is a predictor of the disease/condition; whether any additional testing will be conducted and whether samples will be destroyed at the end of the testing process.

5.7.Costs to the Subject

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). Normally, subjects should not have to pay for research procedures without direct benefit. No charge may be made to subjects if the study costs are already covered by a grant, contract, or other payment method.

5.8.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.

NOTE: The RSRB requires a prorated system for financial payments. This means that payments are accrued as the study progresses and that subjects do not have to complete the entire study to be eligible to receive a payment. This is to protect the subject’s right to withdraw without penalty.

5.9.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.

  1. CONCOMITANT AND DISALLOWED MEDICATIONS

As applicable, describe any required treatments, allowed concomitant medications, or disallowed medications.State, where appropriate, the dosage, frequency, and duration of each treatment the subject is required to take or limited to taking. Indicate if subjects need to stop any medications in order to participate and, if so, how that will be managed.

  1. 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, termination of funding, worsening of the disease under study, intercurrent illness, pregnancy). 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.

  1. STUDY DRUG/DEVICE/BIOLOGIC ADMINISTRATION/ASSIGNMENT

[Note: The IB/package insert/device information sheet, as applicable, should be included in Section 50 of the RSRB application for all protocols that include this section.]