Guidelines for Writing a Research Protocol – Biomedical
(RSRB Protocol Template Final v. 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.
2. 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 Research to 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.
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3. 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 center protocols, 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),
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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.
4. SUBJECT IDENTIFICATION, RECRUITMENT AND CONSENT
4.1. 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).
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
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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 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.
5. 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.
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REGIMEN DESCRIPTION
Agent
Agent X
Premedications;
Precautions
Premedicate with
DRUG for 3 days
prior to Agent X.
Dose
300 mg/m2 in
500 cc NS
Route
IV over 2 hours
before Agent Y
Schedule
Days 1-3,
week 1
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
Cycle
Length
4 weeks
(28
days)
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 and state 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
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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.
6. 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.
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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, 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.
8. 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.]
8.1. Study Drug/Device/Biologic
List all study drugs/devices/biologics (including placebo) and indicate whether they are
investigational. Clarify whether an IND/IDE has been obtained or provide justification why the
product is IND/IDE exempt [FDA 21 CFR 312.2(b)/FDA 21 CFR 812.2(c)]. Indicate who will
supply, package and label them. For study drugs/biologics, list all ingredients and the
formulation and dosage unit(s) of the active study drug(s)/biologic(s) and placebo (where
applicable).
8.2. Dosage of Study Drug/Biologic
State the dosage for all investigational drugs/biologics or test medications. Describe provisions
for the following (as applicable): Dosage initiation titration schedules, dosage reduction (e.g.,
for Adverse Events (AEs)), dosage suspension or rechallenge.
8.3. Subject Enrollment/Randomization
Indicate whether subjects will be randomized and describe the method for assigning study
drug/device/biologic/procedure groups.
8.4. Accountability of Investigational Supplies
Describe plans for control of the drug/device/biologic by indicating who will be responsible for
receipt, storage, dispensing, collection, accountability and disposal of the investigational
supplies (e.g., the pharmacist). This includes maintaining accurate records of supplies received,
used and returned. Indicate if the pharmacist is the unblinded third party. See the OHSP
Investigator Toolkit for a sample drug accountability log.
8.5. Subject Withdrawal of Study Drug
Indicate whether subjects may stop study drug or other treatments and still continue to be
followed in the study, and whether the subject may resume the study drug or treatment after
stopping it.
8.6. Emergency Drug Disclosure
Indicate how drug disclosures will be maintained (e.g., envelopes, labels, electronic system)
and who will receive and maintain this information. A statement should be included noting that
disclosure of the subject’s [envelope or label] should be accessed only in the case of a medical
emergency. If such action is necessary, indicate subsequent required actions that should be
taken by the Investigator and/or pharmacy. Also specify whether subjects will be withdrawn
from the entire study, or from study drug only, should drug disclosure occur.
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9. SAFETY AND REPORTABLE EVENTS
9.1. Adverse Event Definition
The following shaded text is recommended wording as applicable:
An adverse event is any symptom, sign, illness, or experience which develops or worsens
during the course of the study, whether or not the event is considered related to study drug.
9.2. Serious Adverse Event
The following shaded text is recommended wording as applicable:
A serious adverse event is defined as any adverse medical experience that results in any of the
following outcomes:
 death;
 is life-threatening;
 requires inpatient hospitalization or prolongation of existing hospitalization;
 results in persistent or significant disability/incapacity;
 is a congenital anomaly/birth defect; or
 requires medical or surgical intervention to prevent permanent impairment or damage.
9.3. Recording Adverse Events
The following shaded text is recommended wording as applicable:
At each subject visit the site study staff will assess adverse events by recording all voluntary
complaints of the subject and by assessment of clinical and laboratory features. At each study
visit, the subject should be questioned directly regarding the occurrence of any adverse
experience since his/her last visit.
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 investigational product (i.e., drug or device), contributing factors,
and any action taken with respect to the study drug/device.
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.
9.4. 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 RSRB policy regarding the reporting of adverse events.
10. RISK/BENEFIT ASSESSMENT
10.1. 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
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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.
10.2. 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.
10.3. 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.
10.4. 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.
11. 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).
NOTE: To ensure appropriate and adequate encryption of portable devices such as laptops, tablets, memory
sticks, etc., contact University Information Technology for assistance. In addition, the HIPAA website
provides frequently asked questions, or contact the HIPAA privacy officer for assistance.
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
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






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.
12. 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)
13. DATA ANALYSIS AND MONITORING
NOTE: Consultation with a biostatistician to plan the statistical analysis is highly recommended, particularly
for studies involving comparisons of treatments.
13.1. 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.
13.2. 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.
13.3. Data and Safety Monitoring
See RSRB 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).
14. REFERENCES
Provide complete, numbered references for all citations listed in the order that they appear.
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Appendix 1
Schedule of Activities
Visit
Visit Window
Obtain informed consent
Confirm eligibility/Enroll
Medical history and demographics
Vital signs
Blood draw
Urine sample
Ultrasound
Health questionnaire
Concomitant medication review
Study drug dispensed
Study drug returned
Adverse event review
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0
(Screening)
-30 days
X
X
X
X
X
1
2
3
4
5
0 days
(X)
X
15 days
30 days
60 days
90 days
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X