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PROTOCOL TEMPLATE: OBSERVATIONAL STUDY
This protocol template should be used for observational research studies including cohort studies, case-control studies, cross-sectional studies and descriptive studies. There is also a Protocol Template for retrospective Descriptive studies. Observational research might require full board review if the risks of the procedures for monitoring are greater than minimal risk or if they are not included in one or more of the 7 Expedited review categories. See the IRB website for more information about Expedited Review.
https://intranet.research.chop.edu/display/cmtirb/Expedited+Review
Sections that are not applicable can be deleted. If the investigators do not think that a section applies, but are unsure, the section can be filled-in with “not applicable.” Delete the sections in blue or red and save with all “track changes” accepted before submission.
Title: / Complete TitleShort Title / eIRB will request a short title of up to 5 words for tracking purposes
Sponsor:
eIRB Number
Protocol Date:
Amendment 1 Date: / Amendment 4 Date:
Amendment 2 Date: / Amendment 5 Date:
Amendment 3 Date: / Amendment 6 Date:
Study Principal Investigator (if multicenter study with CHOP PI responsible)
Office Address
City, ST, ZIP
Phone XXX-XXX-XXXX
email:
Site Principal Investigator
The Children’s Hospital of Philadelphia
Office Address
Philadelphia, PA, 19104
Phone XXX-XXX-XXXX
email:
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Table of Contents
Table of Contents ii
Abbreviations and Definitions of Terms iv
Abstract v
Protocol Synopsis vi
EXAMPLE: Table 1: Schedule of Study Procedures viii
EXAMPLE: Figure 1: Study Diagram ix
1 Background Information and Rationale 1
1.1 Introduction 1
1.2 Relevant Literature and Data 1
1.3 Compliance Statement 1
2 Study Objectives 1
2.1 Primary Objective (or Aim) 1
2.2 Secondary Objectives (or Aim) 2
2.3 Secondary Objectives (or Aim) 2
3 Investigational plan 2
3.1 General Schema of Study Design 2
3.2 Study Duration, Enrollment and Number of Sites 2
3.3 Total Number of Study Sites/Total Number of Subjects Projected 3
3.3.1 Duration of Study Participation 3
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected 3
3.4 Study Population 3
3.4.1 Inclusion Criteria (examples) 3
3.4.2 Inclusion Criteria 3
3.4.3 Exclusion Criteria 3
4 Study Procedures 5
4.1 Screening Visit 5
4.2 Observational Period (Give this a name relevant to the Study) 5
4.2.1 Visit 1 5
4.2.2 Visit 2 5
4.3 Follow-up Phase (only if applicable) 5
4.4 Follow-up Phase (only if applicable) 6
4.4.1 Visit 6 6
4.4.2 Visit 6: End of Study 6
4.5 Unscheduled Visits 6
4.6 Subject Completion/Withdrawal 6
4.6.1 Early Termination Study Visit 6
5 Study Evaluations and Measurements 7
5.1 Screening and Monitoring Evaluations and Measurements 7
5.1.1 Medical Record Review 7
5.1.2 Physical Examination 7
5.1.3 Vital Signs 7
5.1.4 Laboratory Evaluations 7
5.1.5 Other Evaluations, Measures 8
5.2 Efficacy Evaluations (only if applicable) 8
5.2.1 Diagnostic Tests, Scales, Measures, etc. 8
5.3 Pharmacokinetic Evaluation 8
5.4 Safety Evaluation 8
6 STATISTICAL CONSIDERATIONS 9
6.1 Primary Endpoint 9
6.2 Secondary Endpoints 9
6.3 Control of Bias and Confounding 9
6.4 Statistical Methods 9
6.4.1 Baseline Data 9
6.4.2 Analysis of Primary Outcome of Interest 9
6.4.3 Pharmacokinetic Analysis (only if applicable) 10
6.5 Sample Size and Power 10
6.6 Interim Analysis (only if applicable) 10
7 SAFETY MANAGEMENT 11
7.1 Clinical Adverse Events 11
7.2 Adverse Event Reporting 11
7.3 Definition of an Adverse Event 11
7.4 Definition of a Serious Adverse Event (SAE) 11
7.4.1 Relationship of SAE to study drug or other intervention 12
7.5 IRB/IEC Notification of SAEs and Other Unanticipated Problems 12
7.5.1 Follow-up report 13
7.6 Investigator Reporting of a Serious Adverse Event to Sponsor 13
7.7 Medical Emergencies (if applicable) 13
8 STUDY ADMINISTRATION 14
8.1 Data Collection and Management 14
8.1.1 Data sources (if applicable, for existing records) 14
8.2 Confidentiality 15
8.3 Regulatory and Ethical Considerations 15
8.3.1 Data and Safety Monitoring Plan 15
8.3.2 Risk Assessment 15
8.3.3 Potential Benefits of Study Participation 16
8.3.4 Risk-Benefit Assessment 16
8.4 Recruitment Strategy 16
8.5 Informed Consent/Assent and HIPAA Authorization 16
8.5.1 Waiver of Consent 17
8.5.2 Waiver of Assent 17
8.5.3 Waiver of HIPAA Authorization 17
8.6 Payment to Subjects/Families 18
8.6.1 Reimbursement for travel, parking and meals 18
8.6.2 Payments to parent for time and inconvenience (i.e. compensation) 18
8.6.3 Payments to subject for time, effort and inconvenience (i.e. compensation) 18
8.6.4 Gifts 18
9 PUBLICATION 18
10 References 19
Appendix 20
Be sure to update the Index after the protocol is finalized. In MS Word, update using the INSERT menu, Index and Tables.
Abbreviations and Definitions of Terms
°C / Degrees centigrade
AE / Adverse event
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Abstract
Use JAMA format (http://jama.ama-assn.org/misc/ifora.dtl#Abstracts). Limit to 150 – 200 word abstract, written for lay members. This abstract is used in the IRB database and in the minutes of meetings.
Context: (Background)
Include 1 - 3 sentences about the clinical importance of the condition and the importance of the research question.
Objectives: (primary and important secondary objectives)
State the precise objective or study question
If more than 1 objective, limit to only the key secondary objectives.
Study Design:
Basic design: Randomized controlled trial, cohort study, case-control study, cross-sectional study, etc.
Setting/Participants:
The setting including location (referral or community center) and level of care (inpatient or outpatient)
The number of sites,
The number and description of participants including key eligibility criteria
Study Interventions and Measures:
Study drug, or other intervention and main monitoring procedures
Main study outcome measures (assessments of primary and key secondary endpoints)
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Protocol Synopsis
(Do NOT include a Synopsis if submitting protocol for expedited review)
Study Title /LIMIT SYNOPSIS to no more than 2 - 3 pages. The synopsis should provide a rapid overview of the study for lay members and for members who are not the primary reviewers. Keep the synopsis BRIEF. Use bullet points.
Funder / Grant Agency, Pharmaceutical company, or Departmental funds
Study Rationale / No more than ½ page
Study Objective(s) / Primary
· To determine (obtain, evaluate, verify, etc.) …
Secondary
· To determine (obtain, evaluate, verify, etc.) …
· Etc.
Study Design / Overview of design. Explain the basic design such as parallel group randomized controlled trial, open-label single arm PK study, diagnostic test evaluation, etc.
Subject Population
key criteria for Inclusion and Exclusion: / Inclusion Criteria
1. Subjects age X – X
2. Include main criteria but does not need to be complete, etc.
Exclusion Criteria
1. Subjects with X or Y, etc.
2.
Number Of Subjects / Total Number of Subjects, Total Number at CHOP, Total Number of Sites
Study Duration / Each subject’s participation will last …
The entire study is expected to last….
Study Phases
Screening
Study Treatment
Follow-Up / The study phases listed at the left are examples only. Usually observational studies have at least 2 phases: (1) Screening: screening for eligibility and obtaining consent and (2) Observation Period: measurements made for monitoring subjects once (cross-sectional) or over time (cohort)
Efficacy Evaluations / Primary evaluation measurements that will be used to assess the primary objective
Pharmacokinetic Evaluations / (include only if applicable)
Safety Evaluations / Primary measurements that will be used to assess safety
Statistical And Analytic Plan / Limit to discussion of analysis to primary endpoint and possibly main secondary endpoint
Data And Safety Monitoring Plan / Describe how is responsible for data quality management and ongoing assessment of safety: PI, independent medical monitor, internal safety committee, or DSMB
EXAMPLE: Table 1: Schedule of Study Procedures
Visit Number / 1 / 2 / 3 / 4
Study Days
Informed Consent/Assent / X
Review Inclusion/Exclusion Criteria / X
Demographics/Medical History / X
Physical Examination / X
Vital Signs: BP, HR, RR / X
Height and Weight / X
Pregnancy Test / X
Prior/Concomitant Medications / X
Clinical Laboratory Evaluation / X
Adverse Event Assessment
This table is an example of a schedule of procedures. The Investigator should construct a table based on the procedures in the protocol. If the study involves more than 1 or 2 visits, it is often preferable to include this table as an Appendix to the Consent Form. This simplifies the consent form.
EXAMPLE: Figure 1: Study Diagram
A flow diagram of the study may be relevant to explain the flow of subjects in the trial. An example flow diagram for a prospective cohort study is included as an example below.
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1 Background Information and Rationale
Section 1 should be no more than 3 – 5 pages. Refer the reader to the applicable grant, or attached literature references for more detailed information. If referring to the grant it is helpful to include page citations.
1.1 Introduction
Brief paragraph or two to describe the setting and rationale for the study. The details of the background go into Section 1.2
1.2 Relevant Literature and Data
Overview of the literature and data relevant to the trial and provide background for the trial. Also the relevant literature establishing the validity for scales, evaluation tools etc. The reference citations should be listed at the end in Section 11. It is usual to limit this to 10 (at most 20) key references.
1.3 Compliance Statement
This study will be conducted in full accordance all applicable Children’s Hospital of Philadelphia Research Policies and Procedures and all applicable Federal and state laws and regulations including 45 CFR 46, 21 CFR Parts 50, 54, 56, 312, 314 and 812 and the Good Clinical Practice: Consolidated Guideline approved by the International Conference on Harmonisation (ICH). Note: Only include the sections of Title 21 if the study is regulated by the FDA. Only include ICH compliance if the study will actually comply with these requirements. All episodes of noncompliance will be documented.
The investigators will perform the study in accordance with this protocol, will obtain consent and assent, and will report unanticipated problems involving risks to subjects or others in accordance with The Children’s Hospital of Philadelphia IRB Policies and Procedures and all federal requirements. Collection, recording, and reporting of data will be accurate and will ensure the privacy, health, and welfare of research subjects during and after the study.
2 Study Objectives
State the overall objectives of the study.
The purpose of the study is to determine the (efficacy, relationship, etc) of …. X to Y
2.1 Primary Objective (or Aim)
The primary objective of this study is to determine the whether the XXX (factor of interest, presenting sign, comorbidity, treatment option, etc.) reduces, increases, etc. outcome measure XXX in children X to X years. This should be specific. For example: “to determine if children with asthma whose parents smoke have more ED visits for asthma over a 1 year period compared to children whose parents don’t smoke.”
The primary objective should be both the most important and the objective on which the study sample size is based. Objectives (aims) are usually phrased in some variant of “…to determine…”. Protocols differ from grants in that they do not usually enumerate specific hypotheses. If included, these belong in the Analysis section.
2.2 Secondary Objectives (or Aim)
The secondary objectives are to:
· Determine if there is a relationship between X to Y.
· Determine the pharmacokinetics of drug X (PK studies are observational when the subject is receiving the drug for clinical purposes).
· Etc.
2.3 Secondary Objectives (or Aim)
The secondary objectives are to:
· Describe the indications for tonsillectomy as a function of age.
· Describe the relationship between sex a ED visits for asthma
3 Investigational plan
Section 3 is a brief overview of the study design. In Sections 3.1.1 – 3.1.4 include brief overview of the study phases (Screening, Baseline assessment, Observational Visits, Follow-Up, etc.).
A description of study design should be included, e.g., randomized controlled trial, concurrent or non-concurrent (retrospective) cohort study, case-control study, cross sectional study, pharmocokinetic-pharmacodynamic study, descriptive study, natural history study, evaluation of a diagnostic, etc. Provide a general description here and a general description of the various phases in Sections 3.1.1, 3.1.2, etc.
Reference to Figure of Study Schema and to Table of Procedures as applicable.
3.1 General Schema of Study Design
Observational studies include retrospective or prospective cohort studies, cross sectional studies, case-control studies and some descriptive studies. Retrospective descriptive studies should use the Descriptive Studies Protocol Template
Provide a general overview the study design and the study groups.
3.2 Study Duration, Enrollment and Number of Sites
Duration of study participation for the subject
For retrospective studies provide the date ranges of the records. For example, “Cases will be included if the initial surgery was between 1/1/1995 and 12/31/2005. Follow-up information though 6/1/2006 will be included, as well as history preceding the initial surgery.” Note that the study need not be purely retrospective to qualify for expedited review, however, prospective components will raise questions (to be addressed elsewhere) as to whether consent can be waived and whether some data will be collected specifically for research purposes.
3.3 Total Number of Study Sites/Total Number of Subjects Projected
3.3.1 Duration of Study Participation
This section refers to the duration of the subject’s participation, not the duration of the study. The study duration per subject will be up to XXX days, with up to XXX days screening, up to XXX days Phase 1, up to XXX days Phase 2, and XXX days follow-up.
3.3.2 Total Number of Study Sites/Total Number of Subjects Projected
The study will be conducted at approximately XX investigative sites in the United States and XXXX.
Recruitment will stop when approximately XXX subjects are ….. It is expected that approximately XXX subjects will be enrolled to produce XXXX evaluable subjects.
3.4 Study Population
The study population for every type of study design is defined by Inclusion and Exclusion criteria. A few examples are included below.