Template for Research Study Protocol
Instructions
This protocol template can be used by investigators to develop a research study protocol for investigator initiated studies. It contains sections typically seen in a protocol.However, there are some sections that will not be needed in every study and “N/A” should be used or the section should be deleted.Instructions and/or sample text is provided to generate ideas of what should be included in some of the sections.This should be deleted and substituted with information that pertains to the actual study.Delete this “Instructions” section from your final protocol. It is permissible to rearrange the sections of the protocol if doing so creates a more logical flow for your specific protocol. (Delete highlighted instructions before submission to the IRB)
Study Protocol Title:
Be consistent with the Title throughout your research application, protocol, and IRB documents.
Principal Investigator:
Name, address and complete contact Information including phone number and e-mail address
Research Team:
Co-Investigators:
Protocol Version:
Mm/Dd/Yyyy or any other format. Use this information in the protocol footer and in the IND application, if applicable.
Table of Contents
1.List of Abbreviations:
1.1.Provide commonly used abbreviations and acronyms:
2.Introduction:
2.1.Background Information and Scientific Rationale
2.2.Summary of Previous Pre-clinical Studies/ Relevant Clinical Studies
2.3.Summary of Epidemiological Data
3.Rationale
4.Potential Risks and Benefits
4.1.Potential Risks
4.2.Potential Benefits
5.Study Objectives
5.1.Primary Objective
5.2.Secondary Objectives
6.Study Design
6.1.Subject Selection
6.2.Inclusion Criteria
6.3.Exclusion Criteria
6.4.Sample Size
6.5.Research Design
6.6.Study Outcome Measures (Endpoints)
7.Statistical Analysis Plan
8.Study Procedures
8.1.Subject Recruitment and Screening
8.2.Study Visits
9.Time and event table:
9.1.Study Duration
9.2.Early Withdrawal of Subjects
9.3.Data Collection and Follow-up for Withdrawn Subjects
10.Adverse Event Reporting:
10.1.Adverse Events
10.2.Define any other Serious Adverse Event (SAEs) based on the specifics of the study.
10.3.Recording of Adverse Events
10.4.Notification of Adverse Events
11.Safety Monitoring Plan
11.1.Data Safety Monitoring:
11.2.Data and Safety Monitoring Board
12.Quality Control and Quality Assurance
13.Ethical Considerations
14.Conflict of Interest
15.Funding Source
15.1.Subject Stipends or Payments
16.Publication Plan
17.References
1.List of Abbreviations:
1.1.Provide commonly used abbreviations and acronyms:
FDA / Food and Drug AdministrationGCP / Good Clinical Practice
ICH / International Conference on Harmonization
2.Introduction:
The introduction should open with remarks that state that this document is a clinical research protocol and the described study will be conducted in compliance with the protocol, Good Clinical Practices standards and associated Federal regulations, and all applicable institutional research requirements.The rest of the introduction is broken out into subsections.Example language for the first paragraph under “Introduction”
Sample Text: This document is a protocol for a human research study. This study is to be conducted according to US and international standards of Good Clinical Practice in accordance with applicable Federal regulations, International Conference on Harmonization (ICH) guidelines, and institutional research policies and procedures.
2.1.Background Information and Scientific Rationale
Text ….
2.2.Summary of Previous Pre-clinical Studies/ Relevant Clinical Studies
Summarize the available clinical study data (published or available unpublished data) with relevance to the protocol under construction - if none is available, include a statement that there is no available clinical research data to date on the investigational product.
2.3.Summary of Epidemiological Data
Describe the disease including incidence
3.Rationale
This section is based on your research question. How would you answer the questions and give explanations to your answer? What are the assumptions and relationships?
Justification of your conducting this study based on existing knowledge and your research question.
4.Potential Risks and Benefits
4.1.Potential Risks
Describe potential risks to individuals participating in this study.
4.2.Potential Benefits
Describe potential benefits to the individual research subject as well as the benefits to science for this clinical trial.
Text …..
5.Study Objectives
Text …..
5.1.Primary Objective
Include the details of your primary objective (which is your main purpose of performing this study and should be focused on one question), outcome measures and method by which outcomes will be determined.
Sample Text:To evaluate the efficacy of antibiotics in the treatment of acute bronchitis
5.2.Secondary Objectives
Include secondary objectives which can be two or three can be dependent or independent of the primary objective, outcome measures and method by which secondary outcomes will be determined.
Sample text:To assess patients overall change in symptoms and return to daily activities after 2 weeks of antibiotic treatment to evaluate management and treatment factors as potential predictors of outcome.
6.Study Design
6.1.Subject Selection
Text …..
6.2.Inclusion Criteria
Create a numbered list of criteria subjects must meet to be eligible for study enrollment (e.g. age, gender, target disease, concomitant disease if required, etc.)Generally should include items such as: “subjects are capable of giving informed consent”, or if appropriate, “have an acceptable surrogate capable of giving consent on the subject’s behalf.”
Sample text….
Age 18 – 90
Diagnosis of rheumatoid arthritis within past 2 years
Able to walk 100 yards without stopping
Able to travel to hospital for study visits
Able to follow a 3-step command
6.3.Exclusion Criteria
Create a numbered list of criteria that would exclude a subject from study enrollment.If appropriate, should generally include that subjects cannot be homeless persons, or have active drug/alcohol dependence or abuse history.If exposure to certain medications or treatments at screening is prohibited, that must be noted in the exclusion criteria—if these are also prohibited concomitant medications during the study period that should be noted here as well.
- Sample text:Current cardiovascular disease
- Allergy to penicillin
- Current alcohol/substance abuse or within the past 6 months
- Serious mental illness that might preclude subject’s ability to comply with study treatment
- Life expectancy of less than 1 year
- Lives more than 50 miles from study center
6.4.Sample Size
Include total number of patients for the study including other sites. Include sample size plus an estimate for screen failures.
Describe how the sample size was determined for this study.The sample size should be based upon the primary outcome variable.If the authors have determined that sample size estimation was not necessary, please provide the rationale.
6.5.Research Design
Include the description of study type (double-blinded, placebo-controlled, open/off label,parallel or crossover design, randomized), number of study arms, prospective, retrospective, or observational, survey, or questionnaire.
Type of study and design should be decided on the basis of proposed objectives and theavailability of the resources.
Study Agent, Device, and/or Intervention Description (If applicable)
Include name, dose, frequency, and route of administration, if applicable.This section should contain a description of the investigational product, its make-up, chemical properties and any relevant physical properties, including any available pharmacologic data. (A good example for this section is the “Description” and “Pharmacology” sections for drugs listed in the Physicians’ Desk Reference). Describe the rationale used for selection of the dose for the protocol under construction.This should be based on non-clinical and clinical data available to date.It should include justification for route of administration, dosage, dosage regimen, and dosage period.
SCREENINGWeek 1 / Week 2 / Week 3
Drug X BID x 14 days
Drug Y QD x 21 Days
Instructions / Instructions
6.6.Study Outcome Measures (Endpoints)
In this section, provide a list of the endpoint variables to be studied along with a description (and reference) of the endpoint variable.
Sample Text:Beck Depression Inventory-II (BDI-II):The BDI-II is a 21-item self-report instrument designed to assess symptoms of depression.Each item requires the research subject indicate which of 4 statements bests describes a symptom of depression that the research subject has experienced over the past 2 weeks.
Sample Text:Hemoglobin A1C (HgA1c):Hemoglobin A1c, also known as glycated hemoglobin, or glycohemoglobin, is a laboratory blood test used to provide an average of blood glucose control over a six to 12 week period.
7.Statistical Analysis Plan
Summarize the overall statistical approach to the analysis of the study.The section should contain the key elements of the analysis plan, but should not be a reiteration of a detailed study analysis plan.The full Statistical Analysis Plan can then be a “stand-alone” document that can undergo edits and versioning outside of the protocol and therefore not trigger an IRB re-review with every version or edit –AS LONG AS THE KEY ELEMENTS OF THE ANALYSIS PLAN DO NOT CHANGE. The key elements should be described in this section.
Be clear on primary as well as any applicable secondary analyses for Primary Aims and Secondary Aims.
Sample Text:Demographic and baseline levels of all clinical outcome variables or endpoints will be compared between the four treatment groups using analysis of variance (ANOVA) for comparison of group means.
8.Study Procedures
8.1.Subject Recruitment and Screening
Describe how subjects will be recruited for the study, e.g. from investigator or sub-investigator clinical practices, referring physicians, advertisement, etc.Note in this section that information to be disseminated to subjects (handouts, brochures, etc.) and that any advertisements must be approved by the IRB for the site; include a sample of such information in the attachment section of the protocol.
You may list any screening requirements such as laboratory or diagnostic testing necessary to meet any noted inclusion or exclusion criteria.However, this information should also be listed in the “Study Design/Subject Selection” section of the protocol.
8.2.Study Visits
In this section, describe all the procedures and treatments required at each visit, broken out by visit.Create a study procedures flowchart/table that describes the activities and procedures to be followed at each visit.Include this flowchart/table in the Attachment section and refer to that attachment in this section.
Include a projected start date.
Provide the total length of time participants will remain in the study including the active intervention and follow up period. Include an approximate end date of the study.
8.3.Time and event table:
Please see the example below; list the specific day or days if appropriate, e.g., Day 1, Cycle 1 or Days 1, 7… etc). Please ensure table reconciles with study objectives, and assessments etc.
SAMPLE / Pre-study / Visit 1 (Day 1) / Visit 2(Day 15) / Visit 3
(Day 30) / Off Treatment / Follow-up
Assessment
Informed Consent / X
History and PE / X / X / X / X
Performance Status / X / X / X / X
Toxicity Evaluations / X / X / X
Tumor Measurements / X / X
Chest x-ray / X / X / X
CBC / X / X / X / X / X
Other required labs
Include correlative Procedures (if applicable) / X / X
*Include any necessary notes detailing specifics of procedures outlined in table. . Do not include tests specific to research (and that are not necessary for eligibility) in the Pre-Study column.
8.4.Study Duration
Length of time to enroll human subjects in the study until the completion of the study
Non-standard of care procedures or outcome measures
Include all non-standard of care items that cannot be billed to a third-party payor.
8.5.Early Withdrawal of Subjects
When and How to Withdraw Subjects
Describe the scenarios under which a subject may be withdrawn from the study prior to the expected completion of that subject (e.g. safety reasons, failure of subject to adhere to protocol requirements, subject consent withdrawal, disease progression, etc.)Also, if abrupt termination of study treatment could affect subject safety (e.g. in an antihypertensive study, abrupt withdrawal without other intervention might cause hypertensive rebound), describe procedure to transition subject off the study drug or to alternate therapy.
8.6.Data Collection and Follow-up for Withdrawn Subjects
Even though subjects may be withdrawn prematurely from the study, it is imperative to collect at least survival data on such subjects throughout the protocol defined follow-up period for that subject (though careful thought should be give to the full data set that should to be collected on such subjects to fully support the analysis).Such data is important to the integrity of the final study analysis since early withdrawal could be related to the safety profile of the study drug.If a subject withdraws consent to participate in the study, attempts should be made to obtain permission to record at least survival data up to the protocol-described end of subject follow-up period.It must be a high priority to try to obtain at least survival data on all subjects lost to follow-up and to note what methods should be used before one can state the subject is truly lost to follow-up (e.g. number of phone calls to subject, phone calls to next-of-kin if possible, certified letters, etc.).
9.Adverse Event Reporting:
9.1.Adverse Events
An adverse event (AE) is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study.Inter-current illnesses or injuries should be regarded as adverse events.Abnormal results of diagnostic procedures are considered to be adverse events if the abnormality:
Rresults in study withdrawal
Is associated with a serious adverse event
Is associated with clinical signs or symptoms
Leads to additional treatment or to further diagnostic tests
Is considered by the investigator to be of clinical significance
List all adverse events, and if possible, identify serious adverse events separately.
Serious Adverse Event (SAE): A Serious Adverse Event is defined as an AE meeting one of the following outcomes:
- Death during the period of protocol defined surveillance
- Life Threatening Event (defined as a participant at immediate risk of death at the time of the event)
- Inpatient hospitalization or prolongation of existing hospitalization during the period of protocol defined surveillance
- Results in congenital anomaly or birth defect
- Results in a persistent or significant disability/incapacity
9.2.Define any other Serious Adverse Event (SAEs) based on the specifics of the study.
All adverse events that do not meet any of the criteria for serious should be regarded as non-serious adverse events.
A preexisting condition is one that is present at the start of the study.A preexisting condition should be recorded as an adverse event if the frequency, intensity, or the character of the condition worsens during the study period.
9.3.Recording of Adverse Events
Sample Text:At each contact with the subject, the investigator will seek information on adverse events by specific questioning and, as appropriate, by examination.Information on all adverse events should be recorded immediately in the source document, and also in the appropriate adverse event module of the case report form (CRF).All clearly related signs, symptoms, and abnormal diagnostic procedures results should recorded in the source document, though should be grouped under one diagnosis.
9.4.Notification of Adverse Events
Sample Text: All adverse events will be reported according to the IRB guidelines.
10.Safety Monitoring Plan
10.1.Data Safety Monitoring:
Monitoring is an ongoing review of the study throughout its duration.
The PI is responsible for reporting any reasons outside the planned study design such as noncompliance with the protocol or if there is any delay in the initiation of the study due toadministrative reasons.
Plans for collecting data and protocol compliance should be included
10.2.Data and Safety Monitoring Board
An Internal Data and Safety Monitoring Board (DSMB) is a group of professionals, experienced in clinical care and/or clinical research, assembled to provide additional safety and oversight to a clinical study.This type of oversight committee can include the sponsor and selected investigators, though must include other members who are independent of the study (can include members from within or external to the sponsor or investigator’s institution).The DSMB will look only at blinded data. This section should describe the above noted DSMB attributes.Also include:
If there is no internal DSMB, delete this section.
11.Quality Control and Quality Assurance
Plans for protocol compliance should be included.
Sample text: Quality control procedures for this research study include random selection of data points with comparison between the paper case report form (CRF) and the electronic database record of those same data.We will statistically examine the data with frequency distributions of outcome variables/endpoints to identify outliers or questionable data points that may represent data errors.
12.Ethical Considerations
Identify any ethical concerns and how you will address these.
13.Conflict of Interest
Any investigator who has a conflict of interest with this study (patent ownership, royalties, or financial gain greater than the minimum allowable by their institution, etc.) must have the conflict reviewed by a properly constituted Conflict of Interest Committee with a Committee-sanctioned conflict management plan that has been reviewed and approved by the study sponsor prior to participation in this study.
14.Funding Source
This section should describe how the study will be financed, but should not contain specific dollar amounts (e.g. “This study is financed through a grant from the US National Institute of Health”, or “… a grant from the American Heart Association”, etc.)
14.1.Subject Stipends or Payments
Describe any subject stipend or payment here.If there is no subject stipend/payment, delete this section.
15.Publication Plan
Describe the plan for publication.To the extent possible, roles and responsibilities of each research team member should be determined in advance.Additionally, if the research study will be published, there should be an additional plan that describes assignment of authorship and the contributions of each author.According to the International Committee of Medical Journal Editors:
- The International Committeeof Medical Journal Editors (ICMJE) member journals have adopted a trials-registration policy as a condition for publication.This policy requires that all clinical trials be registered in a public trials registry such as ClinicalTrials.gov, which is sponsored by the National Library of Medicine.Other biomedical journals are considering adopting similar policies.Any clinical trial starting enrollment after July 1, 2005 must be registered either on or before the onset of patient enrollment.
- The ICMJE defines a clinical trial as any research project that prospectively assigns human participants to intervention or comparison groups to study the cause-and-effect relationship between a medical intervention and a health outcome.Studies designed for other purposes, such as to study pharmacokinetics or major toxicity (e.g., Phase 1 trials), would be exempt from this policy.
16.References