THOMASJEFFERSONUNIVERSITY
KimmelCancerCenter
iNSERT tITLE OF THE PROTOCOL
[Include phase (e.g. phase I, phase II, etc.), design (e.g. randomized, double blind, placebo controlled, etc), if the studyis multi-centered, the investigational drug, and target disease(s)]
Example title:
A phase II, randomized, double-blind, placebo-controlled, multi-center study of the effects of XXXX on infarct size in subjects with diabetes mellitus presenting with acute myocardial infarction.
Principal Investigator: / Insert the Name of the Principal InvestigatorInsert Department Name
Insert Address
Insert Phone Number
Co-Investigator(s): / Insert the Name of the Co-Investigator(s)
Insert Department Name
Insert Address
Insert Phone Number
Funding Sponsor: / Insert the Name of Primary Funding Institution
Insert Address
Insert Phone Number
Regulatory Sponsor: / Insert name of IND holder if applicable
IND Number: / Insert IND Number if applicable
Study Product: / Insert Study Drug Name – Generic, followed by marketed name if applicable
Protocol Number: / Insert Protocol Number (e.g. CCRRC number and IRB #)
Version: / Date:
CONFIDENTIAL
This document is confidential and the property of THOMASJEFFERSONUNIVERSITY. No part of it may be transmitted, reproduced, published, or used by other persons without prior written authorization from the study sponsor.
Table of Contents
Study Summary
1Introduction
1.1Specific Aims and Hypothesis
1.2Background
1.3Study Therapy
1.4Preclinical Data
1.5Clinical Data to Date
1.6Dose Rationale and Risk/Benefits
2Study Objectives
2.1Primary Objective
2.2Secondary Objective(s)......
3Study Design
3.1General Design
3.2Primary Study Endpoints
3.3Secondary Study Endpoints
3.4Primary Safety Endpoints
4Subject Selection and Withdrawal
4.1Inclusion Criteria
4.2Exclusion Criteria
4.3Gender/Minority/Pediatric Inclusion for Research
4.4Subject Recruitment and Screening
4.5Early Withdrawal of Subjects
4.5.1When and How to Withdraw Subjects
4.5.2Data Collection and Follow-up for Withdrawn Subjects
5Study Drug/Therapy
5.1Description
5.2Treatment Regimen
5.3Risks
5.4Method for Assigning Subjects to Treatment Groups
5.5Preparation and Administration of Study Drug/therapy
5.6Subject Compliance Monitoring
5.7Prior and Concomitant Therapy
5.8Packaging
5.9Blinding of Study Drug
5.10Receiving, Storage, Dispensing and Return
5.10.1Receipt of Drug Supplies
5.10.2Storage
5.10.3Dispensing of Study Drug
5.10.4Return or Destruction of Study Drug
6Study Procedures
6.1Study Visit Schedule
6.2Definition of Dose Limiting Toxicities
6.3Dose Delays and Dose Modifications.
7Statistical Plan
7.1Sample Size Determination
7.2Statistical Methods
7.3Subject Population(s) for Analysis
8Safety and Adverse Events
8.1Definitions
8.2Recording of Adverse Events
8.3Unblinding Procedures......
8.4Stopping Rules
8.5Data and Safety Monitoring Plan......
8.5.1Medical Monitoring and AE/SAE Reporting
8.5.2Data and Safety Monitoring Committee...... 19
9Data Handling and Record Keeping
9.1Confidentiality
9.2Source Documents
9.3Case Report Forms
9.4Records Retention
10Study Monitoring, Auditing, and Inspecting
10.1Study Monitoring Plan
10.2Auditing and Inspecting
10.2.1Independent External and Internal Audits...... 24
11Ethical Considerations
12Study Finances
12.1Funding Source
12.2Conflict of Interest
12.3Subject Stipends or Payments
13Publication Plan
14References
15APPENDices...... 27
List of Abbreviations
Insert the abbreviation and definition for all abbreviations used throughout protocol.
1
Study Summary
Title / Full title of protocolShort Title / Shortened title, or “Lay title”
Protocol Number / The standard protocol number used to identify this study (e.g. CCRRC # and IRB #)
Phase / Clinical study phase (e.g. Phase 1, 2, 3 or 4)
Methodology/Study Design / Design attributes such as single blind, double blind or open label; Single or Multi-site; Randomized, placebo or active placebo control; cross-over design, etc.
Study Duration / Estimated duration for the main protocol (e.g. from start of screening to last subject processed and finishing the study)
Study Center(s) / Single-center or multi-center. If multi-center, note name of all centers involved.
Objectives / Brief statement of study objectives
Number of Subjects / Number of subjects projected for the entire study (e.g. not for simply one site, rather for entire study, all sites combined).
Diagnosis and Main Inclusion Criteria / Note the main clinical disease state under study and the key inclusion criteria (i.e. not the entire list that will appear later in the protocol –rather only the key inclusion criteria)
Study Therapy, Dose, Route, Regimen / Study drug name (generic name, though can also state marketed name if name-brand used in the study) or other therapy. Also dose, dose route and dose regimen
Duration of administration and follow-up / Total duration of drug product administration (including any open-label lead-in, if applicable), and the duration of follow-up period.
Reference therapy / Note if there is a standard reference therapy against which the study product is being compared, or if the reference is a placebo
Statistical Methodology / A very brief description of the main elements of the statistical methodology to be used in the study. (As few lines as possible).
Schema / Include a brief description of the study schema using a flow diagram
1.0 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 University research requirements. The rest of the introduction is broken out into subsections.
Example language for the first paragraph under “Introduction” and before the section “1.1 Specific Aims”:
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 (FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable government regulations and Institutional research policies and procedures.
1.1Specific Aims and Hypothesis
State the hypothesis and specific aims. List the long-term objectives and what the proposed research will accomplish.
1.2 Background and Rationale
This section should describe the rationale for the current study.Briefly provide the background information leading to this study, evaluate existing knowledge, and identify gaps which this study will fill.
State the importance of the research by relating the specific aims to the long-term objectives.
This section should contain a background discussion of the target disease state to which the investigational product(s) hold promise and any pathophysiology relevant to potential study treatment action.
1.3Study Therapy
This section should contain a description of the investigational product and all other therapies to be used in the trial, along with their make-up, chemical properties and any relevant physical properties, including any available pharmacologic data.
This should also include the class of drug and the mechanism of action if drug trial.
This section should also indicate FDA approval status (e.g. is it a marketed drug/therapy and for what indication)
1.4Preclinical Data
Summarize the available non-clinical data (published or available unpublished data) that could have clinical significance.
1.5Clinical Data to Date
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, and describe method of assessing efficacy and dosage for current trial**
1.6Dose Rationale and Risk/Benefits
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.
Include justification for route of administration, dosage, dosage regimen, and dosage period.
Discuss why the risks to subjects are reasonable in relation to the anticipated benefits and/or knowledge that might reasonably be expected from the results.
2.0 STUDY OBJECTIVES
Describe the overall objectives and purpose of the study. This should include both primary and any secondary objectives, e.g.:
2.1 Primary Objective:
To assess the efficacy of XXXX on (for example) decreasing infarct size as measured by Sestamibi scanning.
2.2 Secondary Objective:
To assess the safety and tolerability of two doses of XXXX in subjects with (for example) acute myocardial infarction.
3.0 STUDY DESIGN
3.1 General Design
Include:
- The type/design of the study (e.g. Phase, randomized, double-blind, parallel group, single or multi-site, etc.)
- A schematic diagram of the trial design, procedures and stages is advisable
- Expected duration of subject participation
- A description of the sequence and duration of all trial periods including follow-up, if any
3.2 Primary Study Endpoints
Describe the primary endpoint to be analyzed in the study (e.g. could be safety or efficacy, depending on the main objective of the study).
3.3 Secondary Study Endpoints
Describe any secondary endpoints to be analyzed in the study
3.4 Primary Safety Endpoints
All studies should include the primary safety endpoints to be measured.
**If the primary objective of the study is a safety study and therefore the Primary Endpoint(s) of the study are safety endpoints, then it should be noted in section 3.1 above and this subsection 3.3 can be deleted**
4.0 SUBJECT SELECTION AND WITHDRAWAL
**If including an eligibility checklist in the appendix, refer to it here**
4.1 Inclusion Criteria
Create a numbered or bulleted list of criteria subjects must meet to be eligible for study enrollment (e.g. age, gender, target disease, concomitant disease if required, etc.)
Generally this 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.”
4.2 Exclusion Criteria
Create a numbered or bulleted 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.
4.3 Gender/Minority/Pediatric Inclusion for Research
All protocols must include documentation of the inclusion of women and minorities in the research protocol.
**If women and minorities are not to be included, provide rationale for exclusion**
4.4Subject Recruitment and Screening
Provide number, age range, and health status of the subject population.
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 any advertisements must be approved by the IRB for the site.
**Include a sample of such information in the attachment section of the protocol**
Also in this section, list any screening requirements such as laboratory or diagnostic testing necessary to meet any noted inclusion or exclusion criteria (greater detail of timing, etc. can be included later in section 6 “Study Procedures” section of the protocol), andidentify sources of research material in the form of specimens, records or data.
**If multi-site trial, also describe patient eligibility verification procedures of sub-site subjects (see below outline)**
**Delete if not a multi-site trial**
Sub-site Procedures
When a potential patient is identified, the TJU Research Nurse/Coordinator should be contacted via email/phone to:
1). Notify them of the pending patient registration
2). Confirm the method of sending registration documents (i.e. fax, email, etc)
3). Communicate the desired timeline of the registration.
The following documentation should be forwarded to the TJU Study Team to confirm eligibility:
1). Signed informed consent form
2). Signed/dated eligibility checklist
3). All Eligibility source documents, Lab Reports/other eligibility scans, tests, etc
Once eligibility has been established, TJU will email the Research Coordinator at the” participating site” to confirm. The subject will then be assigned a registration number. This number is unique to the participant on this trial and must be used moving forward (i.e. for CRF completion, SAE reporting, etc).
A master study enrollment log will be maintained by the study team at the ThomasJeffersonUniversity. The participating site will also be asked to maintain an enrollment/screening log on-site, and fax this information to TJU twice a month to the TJU clinical coordinator.
Patients cannot be registered to this study on the weekends. If a patient is to be registered on a Friday, they will need to contact the TJU Research coordinator by Friday at noon at the latest.
If a patient is enrolled at the participating site, without approval from the coordinating site, TJU will:
1). temporarily suspend the participating site
2). Complete mandatory re-training of staff at the participating site on the enrollment process. This training will be fully documented.
If enrollment without approval occurs a second time, the participating site will not be able to continue to participate in this study.
4.5Early Withdrawal of Subjects
4.5.1 When and How to Withdraw Subjects
Describe the scenarios under which a subject may be withdrawnfrom the study prior 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.
4.5.2 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.).
5.0 STUDY DRUG/THERAPY
5.1 Description
This section should be a very brief synopsis of section 1.3 “Study Therapy” describing the investigational agent or other therapy (e.g. radiation surgery, etc.), along with how the drug product will appear (e.g. as tablets or capsules of “X”mg, as a liquid with “X”mg dissolved in 10ml 5% dextrose and water, etc.) if drug trial.
5.2 Treatment Regimen
Describe dose, route of administration, and treatment duration.
5.3 Risks
Describe risks and assess likelihood and seriousness.
**Please ensure that risks are in agreement with those listed in the Investigator Brochure or, if applicable, the package insert**
**Describe risks as “Likely” (10% or greater) “possible” (3-9%) and “Rare” (less than 2%) in a bulleted list**
Also describe the following:
- Procedures for protecting against or minimizing potential risks.
- Potential benefits and importance to the subjects and others.
- Why risks are reasonable in relation to benefits.
5.4Method for Assigning Subjects to Treatment Groups
Describe how a randomization number and associated treatment assignment will be made. This could be selection of a sequentially numbered drug kit/box, or communication with a randomization center that assigns a number associated with a specific treatment kit/box, etc.
5.5Preparation and Administration of Study Drug/Therapy
Describe in detail all the steps necessary to properly prepare study treatment. Include whether the drug preparation will be done in a pharmacy or by a study team member, if drug trial.
Fully describe how the study treatment is to be administered. If study drug is stored, mixed/prepared or dispensed from the Investigational Drug Service, that should be noted here, including the contact number to that service office. If radiation therapy is being used or surgery is involved, the administration of these procedures should also be described here.
**If company is supplying the drug, this should also be described here (e.g. who is supplying the drug, is it free of charge, method of drug shipment, etc.)**
**If multi-site trial, also include drug supply info and procedures to the sub-site**
5.6Subject Compliance Monitoring
Describe how the study team will assess and track subject compliance with the study treatment regimen, and what procedures must be followed for any subject who is significantly non-compliant with the study treatment regimen.
**If multi-site trial, also briefly describe monitoring of sub-site and actions for non-compliance (see below outline)**
**Delete below if not a multi-site trial**
The participating site will be required to submit all baseline and Cycle 1 Case Report Forms to the Coordinating Site (TJU) Research Nurse/Research Coordinator (215-XXX-XXXX) within 2 weeks of the corresponding visits. Subsequent cycles case report forms (Cycle 2 and beyond) should be submitted via fax within 4 weeks of the corresponding visit.
A separate research chart will be maintained for each subject enrolled at the “participating site”. Case Report Forms will be reviewed and data queries will be issued via email as applicable. All applicable data/forms will be filed in the subject’s research chart accordingly.
The TJU Study Team will conduct a monitoring visit (either on site or via phone) within 4 weeks of the first subject enrollment at the “participating site”. Additional monitoring by the Coordinating Site (TJU) Study Team will take place on an as needed basis only.
The Participating Site will be asked to track all study AEs in a spreadsheet over the course of this study. This information should be kept up-to-date and available upon request by the Coordinating Site, Medical Monitor, or PI. It will be forwarded to the Coordinating Site quarterly for the formal quarterly Medical Monitor Review. A copy of this template AE tracking log is attached.
The TJU Clinical Trial Management System will be used to track patient enrollment and screening information for all patients enrolled on this study at both the Thomas Jefferson University and ”participating site”. No other database systems will be utilized to track patient data for this study.
5.7Prior and Concomitant Therapy
In this section, describe:
- What prior and/or concomitant medical therapy will be collected (if applicable).
- Which concomitant medicines/therapies (including rescue therapies) are permitted during the study
- Which concomitant medicines/therapies are not permitted during the study (if applicable)
5.8Packaging