SPRITES: SERTRALINE PEDIATRIC REGISTRY FOR THE EVALUATION OF SAFETY A NON-INTERVENTIONAL, LONGITUDINAL, COHORT STUDY TO EVALUATE THE EFFECTS OF LONG-TERM SERTRALINE TREATMENT IN CHILDREN AND ADOLESCENTS
Conditions: Obsessive Compulsive Disorder
Sponsor: Pfizer's Upjohn has merged with Mylan to form Viatris Inc.

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SPRITES: SERTRALINE PEDIATRIC REGISTRY FOR THE EVALUATION OF 
SAFETY 
A Non-interventional, Longitudinal, Cohort Study to Evaluate
the Effects of Long-term Sertraline Treatment in Children and Adolescents
Compound Name:
Sertraline
Protocol Number:
A0501093
Phase:
4
Version and Date:
Final Protocol Amendment 5
24 October 2019
This document contains confidential information belonging to Pfizer, Inc. Except as otherwise 
agreed to in writing, by accepting or reviewing this document, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it 
for unauthorized purposes. In the event of any actual or suspected breach of this obligation, Pfizer, 
Inc. must be promptly notified.

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PROTOCOL SUMMARY
This prospective, longitudinal, cohort study is intended to evaluate the risks and benefits of 
up to 3 years of treatment with sertraline in subjects age 6 to 16 (inclusive).
The primary objectives are to evaluate the long-term impact of treatment with sertraline on 
aspects of cognition, emotional and physical development, and pubertal maturation. In order
to further evaluate the relative risks and benefits of long-term sertraline exposure, a 
secondary objective is to evaluate the differential effect of sertraline on cognitive and
emotional development and physical and pubertal maturation over time stratified by 
pre-specified covariates (ie, demographics, previous treatment with psychotropic 
medications).
A total of 900 subjects (720 exposed to sertraline as prescribed by their physician [with or 
without psychotherapy] and 180 exposed to psychotherapy alone) age 6 to 16 (inclusive) will 
be enrolled in the study. Study visits will take place at baseline, 12 weeks, 6 months, and 
every 6 months thereafter for 3 years. At each study visit, cognition, emotional and physical 
development, and pubertal maturation will be assessed using the following measures: (1) for
cognition, Trails B, an objective measure of executive functioning, and the Metacognition 
Index from the Behavior Rating Inventory of Executive Function (BRIEF); (2) for 
behavioral/emotion regulation, the Behavioral Regulation Index from the BRIEF; and (3), for 
physical development and pubertal maturation, standardized ascertainment of height/weight 
and pubertal staging, eg, Tanner or Pubertal Development Scale (PDS). Sertraline exposure, 
reasons for dose adjustment, estimated compliance, and concomitant medications will be 
ascertained at each study visit.  Statistical analyses will include examination of a 
dose-response relationship between sertraline and each outcome domain; and comparison of
sertraline-exposed and unexposed subjects on each outcome domain.  
Clinicians will be asked to monitor subjects closely for any indications of suicidal feelings, 
behavior changes, or other signs of clinical deterioration. At each study visit, adverse events
(AEs), serious adverse events (SAEs), and suicidal events will be systematically assessed; 
SAEs will be reported to the Pfizer Safety Database, and suicidal events will be ascertained 
using the Columbia-Suicide Severity Rating Scale (C-SSRS).  
Sertraline will be prescribed according to usual and customary “real world” practice by 
physicians and allied health professionals in clinical practices. 
SPRITES is expected to add meaningful information on the safety of long-term sertraline use 
in pediatric subjects and to elucidate its potential to affect cognition, emotional and physical 
development, and pubertal maturation.

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SCHEDULE OF ASSESSMENTS
Study Visits
Assessment
Baseline1
3-month 
Visit
6-month 
Visit
12-month 
Visit
18-month 
Visit
24-month 
Visit
30-month 
Visit
36-month 
Visit
Sertraline exposure2
X
X
X
X
X
X
X
X
Diagnoses
X
X
X
X
X
X
X
X
Concomitant medications
X
X
X
X
X
X
X
X
Mental status (CGI-S)
X
X
X
X
X
X
X
X
Mental status (CGI-I , CGI-T, CGI-E)
NA
X
X
X
X
X
X
X
Function (CGAS)
X
X
X
X
X
X
X
X
All Adverse Events (including PAERS)3
X
X
X
X
X
X
X
X
Suicidal Events (C-SSRS)3
X
X
X
X
X
X
X
X
Serious Adverse Events (SAEs)4
X
X
X
X
X
X
X
X
Trails B
X
X
X
X
X
X
X
X
BRIEF (cognition)
X
X
X
X
X
X
X
X
BRIEF (behavior/emotional regulation)
X
X
X
X
X
X
X
X
HoNOSCA
X
X
X
X
X
X
X
X
Height and weight
X
X
X
X
X
X
X
X
Pubertal stage, assessed by the PDS/Tanner Staging
X
X
X
X
X
X
X
X
Selected predictor variables5
X
X
X
X
X
X
X
X
CGI-S=Clinical Global Impression-Severity; CGI-I=Clinical Global Impression-Improvement at post-baseline visits only; CGI-T=Clinical Global Impression-Tolerability; 
CGI-E=Clinical Global Impression-Effectiveness; CGAS=Child Global Assessment Schedule; PAERS=Pediatric Adverse Event Rating Scale; C-SSRS= Columbia-Suicide 
Severity Rating Scale; BRIEF=Behavior Rating Inventory of Executive Function; HoNOSCA=Health of the Nation Outcome Scale for Children and Adolescents; PDS=Pubertal 
Development Scale.
1.
Baseline defined as prior to or within 45 days of initiating treatment (if exposed) and after providing parental/guardian permission and assent, when required.
2.
Sertraline exposure defined by dose, duration and compliance.
3.
Includes new or worsening suicidal ideation, an interrupted suicide attempt, an aborted suicide attempt, preparatory acts or behavior towards making a 
suicide attempt, an actual suicide attempt or completed suicide. The Baseline C-SSRS will assess lifetime risk while the C-SSRS for all other visits will 
assess suicidality since the subject’s last visit.  
4.
SAEs will be reported on a by-visit basis using Pfizer’s SAE reporting system and will be screened and cross-checked at study visits.  For a SAE involving a 
suicidal event, the clinician will complete questions that comprise the SAE CRF module (SAE HARM 1, SAE HARM 2, and SAE CGI_CGAS).  The 
clinician will ensure that a C-SSRS is completed as part of either a scheduled or unscheduled visit, but not both, and captures suicidal ideation and suicidal 
behavior experienced by the patient since his/her last visit.
5.
For example: subject height/weight, diagnosis, comorbidity, and other potential moderators of treatment outcome.

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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................6
1. INTRODUCTION .................................................................................................................9
1.1. Overall Aim of SPRITES..........................................................................................9
1.2. Background and Rationale ........................................................................................9
2. STUDY OBJECTIVES........................................................................................................10
3. STUDY DESIGN.................................................................................................................10
3.1. Overview .................................................................................................................10
4. SUBJECT SELECTION......................................................................................................10
4.1. Inclusion Criteria for All Subjects ..........................................................................11
4.2. Exclusion Criteria for All Subjects .........................................................................12
5. STUDY TREATMENTS.....................................................................................................14
5.1. Allocation to Treatment ..........................................................................................14
5.2. Drug Information.....................................................................................................14
5.3. Drug Supplies..........................................................................................................15
5.4. Concomitant Medications .......................................................................................15
6. STUDY PROCEDURES .....................................................................................................15
6.1. Enrollment...............................................................................................................15
6.1.1. Duration of Enrollment...............................................................................15
6.1.2. Screening ....................................................................................................15
6.2. Study Period ............................................................................................................15
6.2.1. Baseline Visit..............................................................................................15
6.2.2. Post-baseline Visits.....................................................................................16
6.2.3. Study Follow-Up ........................................................................................17
6.3. End-of-Study Form .................................................................................................17
6.4. Withdrawal of Parental/Guardian Permission/Assent.............................................17
7. OUTCOME ASSESSMENTS.............................................................................................17
7.1. Primary Outcome Assessments...............................................................................17
7.1.1. Cognitive Development..............................................................................18
7.1.1.1. Objective Measure of Cognitive Function (Trails B)................18
7.1.1.2. Behavior Rating Inventory of Executive Function 
(BRIEF) .............................................................................................18

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7.1.2. Cognitive and Emotional Development......................................................18
7.1.3. Height and Weight......................................................................................18
7.1.4. Pubertal Maturation ....................................................................................18
7.2. Secondary Outcome Assessments...........................................................................19
7.3. Possible Risk and Benefit of Assessments..............................................................21
8. ADVERSE EVENT REPORTING......................................................................................21
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................31
9.1. Power/Sample Size Estimates .................................................................................31
9.2. Analysis Plan...........................................................................................................31
9.2.1. Descriptive Analysis of Primary Outcome Measures.................................31
9.2.2. Marginal Structural Model (MSM) Analysis of Primary Outcome
Measures ..........................................................................................................32
9.3. Methods to Control for Potential Limitations .........................................................33
9.4. Sensitivity Analyses ................................................................................................33
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................33
11. DATA HANDLING AND RECORD KEEPING .............................................................33
12. ETHICS..............................................................................................................................34
12.1. Institutional Review Board/Independent Ethics Committee.................................34
12.1.1. Study Approval.........................................................................................34
12.1.2. Amendments to the Protocol ....................................................................34
12.2. Ethical Conduct of the Study ................................................................................35
12.3. Subject Information and parental/guardian permission/assent..............................35
12.3.1. Subject Information ..................................................................................35
12.3.2. Parental/guardian permission/assent.........................................................36
12.4. Confidentiality.......................................................................................................36
12.5. Authorization for Use and Disclosure of Protected Health Information 
(Health Insurance Portability and Accountability Act).............................................37
12.6. Cost to Subjects.....................................................................................................38
13. DEFINITION OF END OF STUDY.................................................................................38
14. SPONSOR DISCONTINUATION CRITERIA ................................................................38
15. PUBLICATION OF STUDY RESULTS..........................................................................38
16. STUDY GOVERNANCE..................................................................................................39
17. REFERENCES ..................................................................................................................40

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LIST OF TABLES
Table 1.
Clinical Global Impression–Effectiveness Scoring..................................20

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List of Abbreviations
AACAP
American Academy of Child and Adolescent Psychiatry 
ADHD
Attention Deficit Hyperactivity Disorder
AE
Adverse Event 
ASK
Antidepressant Safety in Kids Study
BRIEF
Behavior Rating Inventory of Executive Function
BMI
Body Mass Index
CAMS
Child/Anxiety Multimodal Study
CAPTN
Child and Adolescent Psychiatry Trials Network 
CBT
Cognitive Behavioral Therapy
C-CASA
Columbia Classification Suicide Assessment
CGAS
Child Global Assessment Schedule 
CGI
Clinical Global Impression
CGI-E
Clinical Global Impression—Effectiveness 
CGI-I
Clinical Global Impression—Improvement 
CGI-S
Clinical Global Impression—Severity
CGI-T
Clinical Global Impression—Tolerability 
CNS
Central Nervous System
CRF
Case Report Form 
C-SSRS
Columbia-Suicide Severity Rating Scale
DCRI
Duke Clinical Research Institute 
eCRF
Electronic Case Report Form
EDC SYSTEM
Electronic Data Collection System 
EDP
Exposure during Pregnancy
EIU
Exposure in Utero 
EMA
European Medicines Agency
FDA
Food and Drug Administration (U.S.)
GCP
Good Clinical Practice 
HIPAA
Health Insurance Portability and Accountability Act
HoNOSCA
Health of the Nation Outcome Scale for Children and Adolescents
ICH
International Conference on Harmonisation 
IEC
Independent Ethics Committee 
IRB
Institutional Review Board
MAR
Missing at Random 

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MCAR
Missing Completely at Random
MDD
Major Depressive Disorder 
MedDRA
Medical Dictionary for Regulatory Activities 
MOP
Manual of Procedures
MSM
Marginal Structural Model
NHANES
National Health and Nutrician Examination Survey
NHS
National Health Service
NIMH
National Institute of Mental Health
NNH
Number Needed to Harm 
NNT
Number Needed to Treat
NOS
Not Otherwise Specified
OCD
Obsessive Compulsive Disorder 
OTC
Over The Counter
PAERS
Pediatric Adverse Event Rating Scale 
PDS
Pubertal Development Scale 
PHI
Protected Health Information 
PTSD
Post-Traumatic Stress Disorder
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SNRI
Serotonin Noradrenaline Reuptake Inhibitor 
SPRITES
Sertraline Pediatric Registry for the Evaluation of Safety
SSRI
Selective Serotonin Reuptake Inhibitor 
TADS
Treatment for Adolescents with Depression Study

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1. INTRODUCTION
1.1. Overall Aim of SPRITES
The overall aim of SPRITES is to evaluate the risks and benefits of long-term sertraline 
treatment on cognition, emotional and physical development, and pubertal maturation in 
pediatric subjects. This study is a component of a post-approval regulatory commitment to 
the European Medicines Agency. SPRITES is intended to reflect outcomes that occur in 
real-world clinical practice.
1.2. Background and Rationale
In 2003, approximately 2% of children and adolescents in the United States were receiving a 
selective serotonin reuptake inhibitor (SSRI) antidepressant.1, 2 Similar numbers have been 
reported by Zito and Safer,3 Zito et al.,4 Safer et al.,5 and Olfson6 et al for various years 
during the 1990s and 2000s. In preschoolers, Zito and colleagues reported that the use of
antidepressants was 3.2 per 1000, or 0.3%, in 1995.7
In a recent review, we examined the balance between the benefits of treatment and the risk of 
suicidality in children and adolescents in multicenter, randomized, controlled trials of 
sertraline versus placebo.8 The published literature was searched for multicenter, 
randomized, placebo-controlled trials of sertraline for pediatric mental disorders. Four 
acute-treatment trials were identified: 2 (pooled) in pediatric major depressive disorder 
(MDD)9 and 2 in obsessive-compulsive disorder (OCD).10,11 Using intent-to-treat analysis 
populations, we calculated the number needed to treat (NNT) for response and remission and 
the number needed to harm (NNH) for suicidality, and their ratio, for each clinical trial. The 
NNT ranged from 2 to 10, indicating clinically meaningful benefits. Benefit was greater for 
OCD than for MDD, and for adolescents compared with children. No age effect was 
apparent for OCD. Suicidality, ascertained by clinical report, was reported in 8 subjects: 
5 assigned to sertraline and 3 assigned to placebo. All but 1 (a placebo-treated subject in the 
Pfizer, Inc. OCD trial10) were enrolled in the sertraline MDD trial.12 The NNH for suicidality 
in MDD was 64. Treatment-emergent suicidality was more common in children (NNH 28.7) 
than in adolescents (NNH 706.3). Since no subject developed suicidality in sertraline-treated 
OCD subjects, the NNH for sertraline in OCD approaches infinity. 
In December of 2008, we extended these findings in the National Institute of Mental Health 
(NIMH)-funded Child/Anxiety Multimodal Study (CAMS),13 in which 488 children and 
adolescents with a primary diagnosis of separation anxiety disorder, generalized anxiety 
disorder, or social phobia were to receive 14 sessions of cognitive behavioral therapy, 
sertraline (at a dose of up to 200 mg per day), a combination of sertraline and cognitive 
behavioral therapy, or a placebo drug for 12 weeks. The percentages of children who were 
rated as very much or much improved on the Clinician Global Impression-Improvement 
(CGI-I) scale were 80.7% for combination therapy (P < 0.001), 59.7% for cognitive 
behavioral therapy (P < 0.001), and 54.9% for sertraline (P < 0.001); all therapies were 
superior to placebo (23.7%). Combination therapy was superior to both monotherapies 
(P < 0.001). Adverse events (AEs), including suicidal and homicidal ideation, were no more 
frequent in the sertraline group than in the placebo group. There were no suicidal events. 

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Taken together, these studies indicate a positive benefit-to-risk ratio for short-term treatment 
with sertraline in adolescents with MDD and in patients of all ages with anxiety and OCDs. 
Additionally, suicidal events appear to be more common in patients receiving sertraline for 
depression than for anxiety disorders or OCD.  
In contrast to short-term effectiveness, the long-term impact (eg, potentially beneficial, 
neutral, or deleterious) of exposure to sertraline on physical, cognitive, and emotional 
development has not been systematically explored in the context of benefits and tolerability 
of sertraline in children and adolescents. 
2. STUDY OBJECTIVES
This prospective cohort study will evaluate the risks and benefits of treatment with sertraline 
under real-world conditions in subjects age 6 to 16 (inclusive) who are prescribed sertraline 
by their physician for up to a 3-year period and who meet all inclusion and none of the 
exclusion criteria for SPRITES. Primary objectives are to evaluate the long-term impact of 
treatment with sertraline on cognition, emotional and physical development, and pubertal 
maturation. In order to further evaluate the relative risks and benefits of long-term sertraline 
exposure, a secondary objective is to evaluate the differential effect of sertraline on cognitive 
and emotional development and physical and pubertal maturation over time stratified by 
pre-specified covariates (ie, demographics, previous treatment with psychotropic 
medications).
3. STUDY DESIGN
3.1. Overview
SPRITES is a non-interventional, prospective cohort study in pediatric subjects exposed and 
unexposed to sertraline followed for a maximum of 3 years. 
4. SUBJECT SELECTION
SPRITES will recruit 900 children age 6 to 16 (inclusive) who are exposed to sertraline
(n=720) (with or without psychotherapy) and 180 exposed to psychotherapy alone under real-
world conditions from approximately 50 US centers in various clinical settings, including the 
Child and Adolescent Psychiatry Trials Network (CAPTN). 
CAPTN began in 2003 as an NIMH-funded practical clinical trials network in pediatric 
psychiatry. Even after NIMH funding ended, the network was intended to be operational 
with support from the Duke Clinical Research Institute (DCRI) for the duration of SPRITES.  
The study includes sites that were formerly part of CAPTN and non-CAPTN sites. The 
overall goal of CAPTN was to evaluate the effectiveness and safety of treatments delivered 
under usual clinical conditions to children and adolescents with major mental illness.  
CAPTN specifically focused on the effectiveness of acute treatments, head-to-head 
comparisons of active treatments, methods for combining Cognitive Behavioral Therapy 
(CBT) with medication, improving partial response with adjunctive or augmentative 
treatments, testing adaptive treatment strategies, maintenance and discontinuation of 
treatment, transportability of treatments from the research to the clinical setting, moderator 
trials, biomarker/biosignature identification and validation, and all aspects of drug safety.  

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With approximately 100 investigators throughout the US and Canada plus more than fifteen 
child psychiatry training programs, CAPTN met the definition of a practical clinical trials 
network, namely real doctors treating real patients in real practice settings.  Eighty percent of 
CAPTN investigators were in solo or group private practice; 20% were from academic 
centers, including those from the CAPTN training programs.  SPRITES sites will include 
allied health professionals who will be able and willing to enroll subjects into the 
psychotherapy arm of the study and who will provide psychotherapy, when indicated, to
subjects enrolled in the medication arm of SPRITES. CAPTN patients spanned the range of 
diagnoses, patterns of comorbidity, and drug and psychosocial treatments.  CAPTN recently 
completed the Antidepressant Safety in Kids (ASK) study (NCT00395213), which informs 
and strongly resembles some aspects of SPRITES. The ASK study is a prospective, 
longitudinal, cohort “safety registry” study of predictors of benefits and AEs in 500+ youth 
with a depressive, anxiety, obsessive-compulsive, or eating disorder exposed to a selective 
serotonin reuptake inhibitor (SSRI) or serotonin noradrenaline reuptake inhibitor (SNRI). 
Each SPRITES investigator will recruit approximately 20-40 subjects identified in standard 
clinical settings as needing treatment with sertraline. All SPRITES sites will be clinical sites 
such that subjects will be recruited from patients seen for clinical care within the practice.  
For sites with multiple investigators and/or good data quality, up to 200 subjects may be 
enrolled per site.
The accessible population is children meeting inclusion/exclusion criteria in the catchment 
area for the study sites.  From these, the study-eligible population will comprise an inception 
cohort of enrolled subjects beginning treatment with sertraline or initiation of psychotherapy 
according to their clinician’s practice. 
To minimize attrition including unequal attrition between study groups, SPRITES will 
include provisions for enhancing sample maintenance adapted from attrition prevention 
strategies used in the Treatment for Adolescents with Depression Study (TADS). [available 
at https://trialweb.dcri.duke.edu/tads].
4.1. Inclusion Criteria for All Subjects
To be eligible for enrollment, the subject must meet all of the following criteria:
1. The subject and the parent must understand the nature of the study and be able to 
comply with protocol requirements. The parent must provide written permission and 
the subject must provide written assent per local IRB requirements.
2. Male or female age 6 to 16 (inclusive) on the day of parental/guardian 
permission/assent.
3. English-or Spanish-speaking.
4. Receiving treatment in an outpatient setting. 

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5. May be receiving stable treatment with another drug or psychosocial intervention 
except as noted in the study exclusion criteria.  For this study, stability is defined as 
no change in dose or form of drug or psychosocial treatment for at least 2 weeks at 
the time of parental/guardian permission/assent. Subjects in the sertraline arm may 
also receive stable treatment with a psychosocial intervention (as defined above) or 
may begin both sertraline and a psychosocial intervention simultaneously, ie, within 
2 weeks.
6. Parents/guardians must be able to complete the BRIEF, which will be offered in 
English and Spanish. All other treatment and study-specific assessments may be 
obtained independent of language if the treatment provider and the person 
administering the test are fluent speakers in the subject’s/parent’s native language.
7. Subject has no plans to move out of the area and expects to remain in contact with the 
treating clinic for the duration of the study.
Sertraline-Exposed Subjects only:
8. Provided a new prescription for sertraline and treatment initiated at baseline or within 
45 days of enrollment in SPRITES.
9. Subject is expected to remain on sertraline beyond initial acute treatment response, 
defined as change from baseline.
Non-exposed Comparison Subjects only:
10. Initiating psychosocial rather than pharmacological treatment for the same spectrum 
of mental health diseases that would be appropriately treated with an SSRI 
medication on or within 45 days of enrollment in SPRITES.
11. Not taking sertraline nor have failed a trial of sertraline judged adequate in dose and 
duration.
4.2. Exclusion Criteria for All Subjects
The subject will not be eligible for enrollment if he or she meets any of the following criteria:
1. Subject or family is unable or unwilling to comply with the protocol.
2. In the opinion of the study investigator, subject is at high and imminent risk of a 
suicidal event at study entry.
3. Subject is taking an antidepressant medication other than sertraline, eg, serotonin 
reuptake inhibitor, serotonin norepinephrine reuptake inhibitor, serotonin 
norepinephrine dopamine triple reuptake inhibitor, bupropion, mirtazapine, 
milnacepran, monoamine oxidase inhibitor, glutaminergic modulator (such as
ketamine, N-acetyl cysteine), any other marketed antidepressant medications or an 

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Over The Counter (OTC) antidepressant medication (such as St. John’s Wort, 
S-adenosyl methionine, etc).
4. Subject has failed two or more trials of an SSRI where the SSRI regimen was judged 
to be adequate in dose and duration (defined as 8 weeks at a fluoxetine equivalent 
dose of 20 mg daily).
5. Subject has a current or past diagnosis of bipolar disorder, schizoaffective disorder,
schizophrenia, or psychosis NOS or has a history of psychosis or is psychotic at study
entry.
6. Subject has a current diagnosis of anorexia nervosa, bulimia, or eating disorder NOS.
7. Subject has a diagnosis of severe autism that would interfere with study conduct or 
with the interpretation of the study assessments. 
8. Subject has a diagnosis of post-traumatic stress disorder.
9. Subject is receiving sertraline for a medical condition, eg, late luteal phase dysphoric
disorder or other menstrual related problems, sexual problems such as premature 
ejaculation, or refractory syncope.
10. Subject with significant mental retardation that would interfere with study conduct or 
with the interpretation of the study assessments.
11. Subject has a co-occurring medical condition that (1) interferes with study 
participation, eg, by constraining treatment with sertraline or necessitating 
hospitalization or surgery, or that (2) impacts cognitive, emotional, social or physical 
development. 
12. Subject is taking one of the following medications: a first or second generation 
antipsychotic, lithium, lamotrigine or other antiepileptic medication, a chronic 
benzodiazepine, or atomoxetine.
13. Subject is taking a psychostimulant.  
14. Subject is taking a medication that has been shown to commonly cause sustained 
adverse effects on cognition, emotion regulation and/or growth and development.
15. Subject has a substance abuse or dependence disorder with the exception of nicotine.
16. Subject has been exposed to another investigational agent within the prior 30 days or 
5 half-lives of the investigational agent, whichever is longer.
Sertraline-Exposed Subjects only:
17. Subject has demonstrated lack of benefit from or intolerance to sertraline.

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18. Subject has demonstrated hypersensitivity to sertraline.
19. Subject is taking a concomitant medication for which a serious concern exists 
regarding an adverse drug-drug interaction with sertraline.
Non-exposed Comparison Subjects only:
20. Have failed a previous adequate course of the type of psychotherapy being considered 
for SPRITES within the past two years of study entry. 
5. STUDY TREATMENTS
5.1. Allocation to Treatment
SPRITES is a non-interventional study focused on the collection of subject data during 
clinical treatment with sertraline and/or psychosocial treatment.  SPRITES does not in any 
way constrain the nature of the treatment administered, which, except for the requirements 
presented in the inclusion/exclusion criteria, is left to doctor, subject, and family preference.
Sertraline administration will be conducted in accordance with usual and customary “real 
world’ practice at each participating site.  The single safety reference document is the US 
Product Label30 [see Manual of Procedures (MOP)]. While many if not most of the subjects
receiving sertraline also will receive cognitive-behavioral psychotherapy, some will receive
other forms of psychotherapy.  For children receiving psychotherapy alone, subjects 
beginning any of the available forms of psychotherapy will be eligible to enroll in SPRITES.
SPRITES recommends that treatment be conducted in a fashion that is consistent with good 
clinical practice (GCP) recommendations as outlined in the patient information materials 
“Facts for Families” from the American Academy of Child and Adolescent Psychiatry 
(AACAP).  At the option of the treating clinician, patient information materials from the 
AACAP “Facts for Families” series covering the use of antidepressant medications may be 
provided to the subject and parent and be reviewed during the parental/guardian 
permission/assent process. 
5.2. Drug Information
Sertraline is an oral antidepressant drug of the SSRI type. Sertraline has 1 active metabolite 
and a lower potential for drug interactions involving CYP2D6 (hepatic cytochrome P-450 
isoenzyme 2D6) than fluoxetine or paroxetine.
Sertraline was originally approved by the Food and Drug Administration (FDA) for treatment 
of major depressive disorder in adults, followed by treatment for OCD and panic disorder. It 
subsequently received approval for treatment of OCD in children age 6 or older. It has since 
been approved for treatment of Post Traumatic Stress Disorder (PTSD) and premenstrual 
dysphoric disorder, and the treatment of social anxiety disorder in adults.

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5.3. Drug Supplies
All SPRITES subjects are clinical patients participating in research, thus there will be 
overlaps with elements of their clinical care. No drug will be supplied as part of the study; if 
prescribed sertraline, subjects will be receiving sertraline as they would in regular clinical 
care.
5.4. Concomitant Medications
Consistent with the fact that SPRITES is a non-interventional study, subjects may be 
receiving stable treatment at baseline with other drug (except as prohibited by the inclusion
and exclusion criteria) or psychosocial interventions and may be prescribed other drug or 
non-drug treatment during the post-baseline course of treatment while enrolled in SPRITES.
6. STUDY PROCEDURES
6.1. Enrollment
A subject is “enrolled” into the study on the date that all eligibility criteria are confirmed.  
Once the SPRITES electronic case report form (eCRF) enrollment form has been completed 
and submitted, a unique subject number will be generated by the system and cannot be 
modified.
6.1.1. Duration of Enrollment
Participation in this study will be up to 3 years.  
6.1.2. Screening
The clinician will first determine whether or not the subject meets the study eligibility 
criteria. Using the SPRITES study enrollment form, all subjects with parental/guardian 
permission/assent for the SPRITES study who meet all inclusion and no exclusion criteria 
will be entered into the eCRF.  Screen Failures will not be entered into the eCRF.
6.2. Study Period
Parental/guardian permission and assent must be obtained before administration of any 
study-specific assessments. The schedule of assessments for the study is provided under 
Section: Protocol Summary. 
6.2.1. Baseline Visit
For subjects receiving sertraline, the baseline visit, which will include routine clinical care
and study assessments, will occur on or within 45 days of initiating treatment with sertraline 
and after obtaining parental/guardian permission and subject assent per local IRB
requirements. For subjects in the psychotherapy group, the baseline visit will occur on or 
within 45 days of initiating treatment and after obtaining parental/guardian 
permission/assent. In addition to the study visit assessment data, the baseline assessment will 

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include collection of information on subject demographics, diagnosis, comorbidity, and other
potential predictors of treatment outcome.
6.2.2. Post-baseline Visits
Post-baseline study assessments will be completed at any study visit whereby the subject is 
still “active” in the study. Active is defined as the family/subject has not withdrawn 
parental/guardian permission/assent or has not been lost to follow-up defined as (1) moved 
with no prospect of continuing in the study, ie, with no local participating center to which the 
subject could transfer or (2) no contact for a period of six months despite three attempts to 
re-contact the subject. 
Post-baseline study assessments, which will include the primary and secondary study 
outcomes, sertraline exposure, as well as selected predictor variables, will occur at 3, 6, 12, 
18, 24, 30, and 36 months. Study assessments will be timed to coincide with treatment visits 
insofar as is possible. Thus, clinicians are encouraged to schedule follow-up visits so that the 
routine visit data and study assessments for those subjects are gathered during or near the key 
post-baseline assessment points, as clinically indicated.
The following will be assessed:
Study Assessments
1. Sertraline exposure (defined by dose, duration, and compliance), where applicable.
2. Objective measure of executive function (Trails B).
3. Function as assessed by Child Global Assessment Schedule (CGAS).
4. Behavior Rating Inventory of Executive Function (BRIEF).
5. Health of the Nation Outcome Scale for Children and Adolescents (HoNOSCA).
6. Height and weight.
7. Pubertal development (Tanner Staging by line drawing or Pubertal Development 
Scale [see 7.1.4]).
8. Adverse Events/Pediatric Adverse Events Rating Scale (PAERS).
9. Columbia-Suicide Severity Rating Scale (C-SSRS).
10. For Serious Adverse Events, the following will be completed:
i.
Pfizer SAE form; and

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ii.
Questions that comprise the SAE Case Report Form (CRF) module 
(SAE HARM 1, SAE HARM 2, and SAE Clinical Global Impression 
(CGI)_CGAS).
Following a SAE involving a suicidal event, the clinician will ensure that a C-SSRS is 
completed as part of either a scheduled or unscheduled visit, but not both, and captures 
suicidal ideation and suicidal behavior experienced by the patient since his/her last visit.
11. Clinical Global Impression (including CGI-S, CGI-I, CGI-T, CGI-E).
12. Comprehensive assessment drawn from selected data elements from the CAPTN Core 
CRF.
6.2.3. Study Follow-Up
Unless parental/guardian permission/subject assent is withdrawn or the subject is lost to 
follow-up, he or she will be followed for the three years of the study and every attempt will 
be made to obtain study assessments.  If a subject discontinues taking sertraline, he or she 
will be followed and treatment status will be documented. Likewise, if a subject in the 
comparison psychotherapy-treated group receives sertraline, another antidepressant, or other 
psychotropic medication, he or she will be followed and treatment status will be documented.  
Site staff should contact the subjects monthly between visits to promote study retention and
assess for SAEs.
6.3. End-of-Study Form
Once a subject has completed the study by (1) exiting early due to withdrawal of 
parental/guardian permission/assent; (2) moving away or for some other reason being unable 
to participate; (3) being lost to follow-up, defined as no contact for six months; or 
(4) completing the full three-year study period, the database system will request a final 
post-study assessment. This form will summarize the study experience, contributing factors 
for the discontinuation (ie, medication non-compliance, adverse event) and will formally 
indicate that no further data for this subject are to be expected. 
6.4. Withdrawal of Parental/Guardian Permission/Assent
All parents/subjects have the right to withdraw at any point during treatment without
prejudice. If parental/guardian permission/assent is withdrawn, procedures performed purely
for the study will stop, and the subject will be considered “inactive” for the purposes of the 
study.  Once parental/guardian permission/assent has been withdrawn, subjects will not be 
eligible to “reenroll” in SPRITES.
7. OUTCOME ASSESSMENTS
7.1. Primary Outcome Assessments
Primary outcome measures will be completed for the study-specific dependent variables at 
specific study visits and include the following.

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7.1.1. Cognitive Development
Cognitive development will be ascertained using a neuropsychological test, Trails B and the 
Metacognition Factor from a neurocognitive test, the BRIEF. 
7.1.1.1. Objective Measure of Cognitive Function (Trails B)
Trails B, which is a set shifting task in which a person draws a line from 1 to A to 2 to B to 
3 to C, etc., is widely used as a measure of executive function in children, adolescents and 
adults.14-17  The subject is instructed to connect the circles as quickly as possible, without 
lifting the pen or pencil from the paper. The subject is timed as he or she connects the "trail." 
If the subject makes an error, and it is pointed out immediately, the subject is allowed to 
correct it. Errors affect the subject's score only in that the correction of errors is included in 
the completion time for the task.  Results are reported as the number of seconds required to 
complete the task; therefore, higher scores reveal greater impairment. Age and gender norms 
are available as are cutoff scores indicating impairment.  
7.1.1.2. Behavior Rating Inventory of Executive Function (BRIEF)
The Behavior Rating Inventory of Executive Function (BRIEF) is a widely used 86 item 
Likert style parent report measure of neurocognitive performance that includes eight 
theoretically and empirically derived subscales: inhibit, shift, emotional control, initiate,
working memory, plan-organize, organization of materials and monitor.18-20  These are 
subsumed in two broad factors: a Behavior Regulation Index consisting of the Inhibit, Shift, 
and Emotional Control subscales, a Metacognition Index consisting of the Working Memory, 
Initiate, Plan/Organize, Organization of Materials, and Task-Monitor scales.  The Behavioral 
Regulation and Metacognition scales taken together comprise a Global Executive Composite 
score.  The BRIEF has excellent internal consistency, test-retest reliability, inter-rater 
reliability, and convergent validity and is age, gender, socioeconomic status, and 
race/ethnicity normed.  
7.1.2. Cognitive and Emotional Development
As the primary measure of cognitive function, SPRITES will employ the Metacognition
Index from the BRIEF.  As the primary measure of behavioral/emotion regulation, SPRITES 
will employ the Behavior Regulation Index from the BRIEF.
7.1.3. Height and Weight
Height, weight and body mass index will be measured and referenced to norms according to 
standardized procedures from the National Health and Nutrition Examination Survey 
(NHANES III).21
7.1.4. Pubertal Maturation
A crucial variable in prospective investigations of development is determination of physical 
and sexual maturation.  In a multi-informant investigations, Dorn et al. (1990)22 and Taylor et
al. (2001)23 found that when boys and girls were shown schematic drawings 
(5 ordinally-scaled drawings/photographs corresponding to the Tanner stages), their 
self-ratings correlated quite well with health-care-provider examination Tanner staging. To 

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avoid intrusiveness in examining for sexual maturity and consequent refusal to provide 
information on pubertal status, we will employ these self-rated pictures for 
teenager/adolescent self-report.  In the event that the subject or parent refuses self-reported
Tanner staging by line drawings and for children 12 and under, we will attempt to use the 
Pubertal Development Scale (PDS). The PDS is a widely used 8-item, gender-specific, 
self-report measure that is able to reliably ascertain pubertal status for children and 
adolescents age 8 to 17.24  The PDS, which was developed for studies in which Tanner 
staging as a procedure is impractical, maps directly on Tanner stage as an index of pubertal 
development.  Hence, irrespective of ascertainment we will report the outcomes for pubertal 
status in Tanner stage units.  Specifically, if the history and physical are consistent with the 
subject’s self report, the clinician will assign a Tanner stage rating.  If they are discrepant, 
eg, the self-report reflects an earlier or later pubertal stage than the clinician believes is 
correct, the clinician will then review the self-report form with the subject and/or parent to 
clarify the subject’s responses. This review will be done in the presence of another person, 
either the parent or a clinic staff member.  At the end of the review, the clinician will then 
assign a best estimate Tanner stage rating.1
7.2. Secondary Outcome Assessments
Secondary outcome measures will be completed for the study-specific dependent variables at 
specific study visits and include the following:

CGI-I;

CGI-T;

CGI-E;

CGI-S;

CGAS;

HoNOSCA.
Note that the HoNOSCA provides a broad view of behavioral symptomatic and functional 
outcomes.  Likewise, the Clinical Global Impressions scores will be “global” in nature and 
not specifically referenced to the symptomatic outcome of SPRITES treatment.  
The NIMH CGI-S and associated CGI scales have become standard rating scales across 
many kinds of studies for both children and adults. The scales allow the clinician rater or 
independent evaluator in a clinical trial to establish both the severity of the subject’s 
condition at baseline and the level of change over time. At baseline, the clinician rater or 
independent evaluator will record the severity of the subject’s condition using the CGI-S, 
                                                
1 Additionally, we note that pubertal development in the U.S. begins as early as age 8 and completes as 
late as age 17. Based on our previous research and the demographic distribution at the CAPTN sites, we expect 
to be able to enroll meaningful numbers of subjects in each age stratum where the transition through puberty is 
operative.

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which will serve as the reference score for the CGI-S, CGI-I, CGI-T, and CGI-E for all post-
baseline visits.  
The CGI-I scale will be used to rate improvement in the subject’s condition (benefits) since 
baseline using the following 7-point scale: 1=very much improved, 2=much improved, 
3=minimally improved, 4=not changed, 5=minimally worse, 6=much worse, 7=very much 
worse. Treatment response for improvement is defined as a CGI-I score of 1 (very much 
improved) or 2 (much improved), whereas treatment nonresponse is defined as CGI-I score 
of 3 to 7 (minimally improved or worse). 
The CGI-T will be used to assess the tolerability of the study medication with respect to 
adverse events. The 7-point rating for the CGI-T will be: 1=very high, 2=high, 3=above 
average, 4=average, 5=low, 6=very low, and 7=extremely low. 
With reference to Table 1 below, the CGI-E is scored as follows. First, the clinician rater 
will identify the degree of therapeutic benefit in the first column. Second, moving across the 
row, the clinician rater will identify the degree to which problems with tolerability adversely 
impact the subject. Third, having selected the terms which best describes the degrees of 
therapeutic benefit and adverse impact, the clinician rater will identify the cell in which 
benefits and adverse impacts intersect: this number will be the subject’s CGI-E score. A 
subject who is much or very much improved and whose adverse impact rating is none or 
mild, ie, a CGI-E score of 1, 2, 5, or 6, will be categorized as a responder. All others will be 
categorized as nonresponders to study medication. 
EXAMPLE: Therapeutic benefit rated as “much improved” and adverse impacts judged “No 
significant interference” yields a CGI-E score of 6, which indicates that this subject is a 
responder. 
Table 1.
Clinical Global Impression–Effectiveness Scoring
Therapeutic Benefit versus
Tolerability/acceptability
No adverse
impact
Mild adverse 
impact
Moderate 
adverse impact
Outweighs 
therapeutic 
effect
Very much improved (CGI-I=1) 
1
2
3
4
Much improved (CGI-I=2)
5
6
7
8
Minimally improved (CGI-I=3)
9
10
11
12
Unchanged or worse (CGI-I 4)
13
14
15
16
CGI-E=Clinical Global Impression-Effectiveness
Shaded=Responder
The Children's Global Assessment Scale (CGAS), a numeric scale (1 through 100), will be 
used to rate the general functioning of the SPRITES study subjects. 
To assess a variety of factors relevant to child mental health, SPRITES employs the 
clinician-rated Health of the Nation Outcome Scale for Children and Adolescents 
(HoNOSCA).25-29 The HoNOSCA has 13 sub-scales, each rated from 0 (no problems) 

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through 4 (severe problems): disruptive or aggressive behavior, Attention Deficit 
Hyperactivity Disorder (ADHD), self-harm, substance abuse, school problems, physical 
illness, psychosis, physical symptoms, internalizing symptoms, peer relationships, self-care, 
family relationships and school attendance problems. Completed by the treating clinician 
using all available information, the HoNOSCA is widely used as both a clinical measure in 
the British National Health Service (NHS) and as a treatment outcome measure in research 
studies, where it shows good to excellent convergent validity, internal and test-retest 
reliability, and change sensitivity. 
7.3. Possible Risk and Benefit of Assessments
This study is a data-collection effort designed according to a “best practice” standard of care. 
There are no anticipated risks of participating in the assessment portions of this study other
than the risk of loss of confidentiality. Some of the questions may be considered repetitive or 
boring or in the case of Tanner self-report, mildly upsetting. The instruments will not replace 
or interfere with the treatment the subject will be receiving. Additional side effects may be 
detected as a result of participating in this study (although there is no way of knowing 
whether the standard method of evaluation would or would not have detected the same side 
effect).
8. ADVERSE EVENT REPORTING
REQUIREMENTS
The table below summarizes the requirements for recording safety events on the electronic 
case report form and for reporting safety events on the non-interventional study (NIS) 
adverse event monitoring (AEM) Report Form to Pfizer Safety.  These requirements are
delineated for three types of events: (1) serious adverse events (SAEs); (2) non-serious AEs
(as applicable); and (3) scenarios involving drug exposure, including exposure during 
pregnancy, exposure during breast feeding, medication error, overdose, misuse, 
extravasation, and occupational exposure.  These requirements apply to all participating 
patients. These events are defined in the section “Definitions of safety events”.
Safety event
Recorded on the 
electronic adverse 
event case report form
Reported on the NIS 
AEM Report Form to 
Pfizer Safety within 
24 hours of awareness
SAE
All
All
Non-serious AE
All
None

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Safety event
Recorded on the 
electronic adverse 
event case report form
Reported on the NIS 
AEM Report Form to 
Pfizer Safety within 
24 hours of awareness
Scenarios involving exposure to a 
drug under study, including
exposure during pregnancy, 
exposure during breast feeding, 
medication error, overdose, misuse, 
extravasation; lack of efficacy; and 
occupational exposure
All (regardless of 
whether associated with 
an AE), except 
occupational exposure
All (regardless of 
whether associated with 
an AE)
For each AE, the investigator must pursue and obtain information adequate both to determine 
the outcome of the adverse event and to assess whether it meets the criteria for classification 
as a SAE (see section "Serious Adverse Events” below)
Safety events listed in the table above must be reported to Pfizer within 24 hours of 
awareness of the event by the investigator regardless of whether the event is determined 
by the investigator to be related to a drug under study. In particular, if the SAE is fatal or 
life-threatening, notification to Pfizer must be made immediately, irrespective of the extent of 
available event information. This timeframe also applies to additional new (follow-up) 
information on previously forwarded safety event reports. In the rare situation that the 
investigator does not become immediately aware of the occurrence of a safety event, the 
investigator must report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the events.
For safety events that are considered serious or that are identified in the far right column of 
the table above that are reportable to Pfizer within 24 hours of awareness, the investigator is
obligated to pursue and to provide any additional information to Pfizer in accordance with 
this 24-hour timeframe. In addition, an investigator may be requested by Pfizer to obtain 
specific follow-up information in an expedited fashion.  This information is more detailed 
than that recorded on the electronic adverse event case report form. In general, this will 
include a description of the adverse event in sufficient detail to allow for a complete medical 
assessment of the case and independent determination of possible causality.  Any information 
relevant to the event, such as concomitant medications and illnesses must be provided.  In the 
case of a patient death, a summary of available autopsy findings must be submitted as soon 
as possible to Pfizer or its designated representative.
The single reference safety document for SPRITES is the Sertraline US product label30 (see 
MOP). 
At each study visit, investigators will solicit any adverse events that occurred since the last 
study visit that meet the AE definition as described in the section below entitled Adverse 
Events.  To support investigators in assessing for AEs that occurred since the previous study 

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visit, the 43 item PAERS in the eCRF will be used as described in the section below titled 
Pediatric Adverse Event Rating Scale (PAERS). 
SPRITES will systematically collect SAEs, as described in the section below entitled Serious 
Adverse Events.  All SAEs will be reported within 24 hours of the site being made aware of 
the SAE using Pfizer’s standard SAE reporting system, via the Pfizer non-interventional 
study SAE report form along with supplemental SPRITES-specific information on the eCRF.  
The subject number assigned by the eCRF will be used as the subject ID on the SAE form.
The FDA recently warned the public about an increased risk of suicidal thoughts and 
behaviors in children and adolescents treated with antidepressant drugs, including those used 
in this study.30,31 The FDA recommends closely monitoring patients who begin taking 
antidepressants for worsening symptoms, suicidal thoughts or feelings, and unusual changes 
in behavior. Families and caregivers are advised to observe the patient closely and 
communicate with the prescribing doctor frequently. As recommended by the FDA, the 
proposed study procedures ask the clinician to observe the subject closely for any indications 
of suicidal feelings, behavior changes, or other signs of clinical deterioration. At the initial 
assessment and throughout the study, psychiatric symptoms, including depressive symptoms 
and possible suicidal ideation (having thoughts or ideas of harming oneself), will be assessed. 
If the subject develops significant suicidal ideation, a preparatory or interrupted suicide 
attempt or makes a suicide attempt at any point during the study, the study doctor will make 
sure that the subject receives appropriate assessment and treatment, which may or may not
include dose adjustment or discontinuation of sertraline. All such events will be classified as 
SAEs and will be reported immediately in two formats: First, the study clinician will 
complete the Pfizer SAE reporting procedure.  Second, the study clinician will complete a
C-SSRS and supplemental data fields on the eCRF established for this purpose.  In addition 
to the C-SSRS and other SAE-specific information, the study clinician will also complete
sections of the study visit assessment package that involve exposure to sertraline and relevant 
secondary outcomes, such as the CGI scores.
Reporting period 
For each patient, the safety event reporting period begins at the time of the patient’s informed 
consent and lasts through the end of the observation period of the study, which must include 
at least 28 calendar days following the last administration of a drug under study; a report 
must be submitted to Pfizer Safety (or its designated representative) for any of the types of 
safety events listed in the table above occurring during this period. If a patient was 
administered a drug under study on the last day of the observation period, then the reporting 
period should be extended for 28 calendar days following the end of observation. Most often, 
the date of informed consent is the same as the date of enrollment. In some situations, there 
may be a lag between the dates of informed consent and enrollment.  In these instances, if a 
patient provides informed consent but is never enrolled in the study (eg, patient changes 
his/her mind about participation), the reporting period ends on the date of the decision to not 
enroll the patient.  

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If the investigator becomes aware of a SAE occurring at any time after completion of the 
study and s/he considers the SAE to be related to sertraline, the SAE also must be reported to 
Pfizer Safety. 
Causality assessment
The investigator is required to assess and record the causal relationship.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of 
each adverse event.  For AEs with a causal relationship to sertraline, follow-up by the 
investigator is required until the event and/or its sequelae resolve or stabilize at a level 
acceptable to the investigator, and Pfizer concurs with that assessment.  
An investigator’s causality assessment is the determination of whether there exists a 
reasonable possibility that sertraline caused or contributed to an adverse event. If the 
investigator’s final determination of causality is “unknown” and s/he cannot determine 
whether sertraline caused the event, the safety event must be reported within 24 hours.  
If the investigator cannot determine the etiology of the event but s/he determines that 
sertraline did not cause the event, this should be clearly documented on the electronic 
Adverse Event Report Form and the NIS AEM Report Form. 
DEFINITIONS OF SAFETY EVENTS
Adverse events
An AE is any untoward medical occurrence in a patient administered a medicinal product.  
The event need not necessarily have a causal relationship with the product treatment or 
usage.  Examples of adverse events include but are not limited to:  

Abnormal test findings (see below for circumstances in which an abnormal test 
finding constitutes an adverse event);

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Lack of efficacy; 

Drug abuse; 

Drug dependency.
Additionally, for medicinal products, they may include the signs or symptoms resulting from:

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
Drug overdose;

Drug withdrawal;

Drug misuse;

Off-label use; 

Drug interactions;

Extravasation;

Exposure during pregnancy;

Exposure during breast feeding;

Medication error;

Occupational exposure.
Abnormal test findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an adverse event are as follows: 

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or

Test result is considered to be an adverse event by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an adverse event.  Any abnormal test result that is determined to be an error does 
not require reporting as an adverse event.
Common adverse events
Adverse events that arise since the patient’s previous visit will be collected at each study visit 
using the 43 item Pediatric Adverse Event Rating Scale (PAERS), contained in the eCRF, 
which was developed as an empirically derived and validated AE monitoring tool that 
provides coverage for common important AEs due to all major classes of Central Nervous 
System (CNS) active medications. The PAERS, which has been reviewed and deemed 
acceptable by the FDA, provides rigorous prospective identification of AEs in a Phase I-IV 

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clinical trial and outcomes research framework. The PAERS allows for (1) simplicity and 
ease of use; (2) clinical applicability to a wide variety of drug exposures; (3) frequency, 
severity, and subjective importance of an AE; and (4) empirically-derived, psychometrically 
validated item content. There are four PAERS forms: (1) a child PAERS, (2) a parent 
PAERS, (3) a clinician PAERS, and (4) a PAERS clinician interview form. SPRITES will
use the PAERS Clinician Interview format in which the PAERs is deployed as a 
semi-structured interview in which the physician does a careful verbal review of all PAERS 
items with the child and the parent. To make the interview version of the PAERS easy to 
administer and to code, the PAERS Clinician Interview form includes the child probe 
questions as well as the MedDRA coded clinician item wording so that the interviewer uses 
child friendly language to ask questions while the construct being measured is captured in 
MedDRA terminology. 
Given the extended period of time between study visits, the PAERS is a required tool that 
helps facilitate the investigator in ascertaining common AEs that may have occurred since 
the previous study visit.  The PAERS eCRF will also be used to collect all AEs since the 
previous visit.
The PAERS clinician form covers the following domains of interest relative to each AE: 
presence in the past week, resolution, severity, causality, and impact on function. AE 
severity and AE-associated functional impairment will be tracked on a five point Likert 
scale: none, mild, moderate, severe, and extreme.
Serious adverse events
A serious adverse event is any untoward medical occurrence in a patient administered a 
medicinal or nutritional product (including pediatric formulas) at any dose that:

Results in death;

Is life-threatening;

Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events);

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the patient or may require intervention to prevent one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious.

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Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
Additionally, any suspected transmission via a Pfizer product of an infectious agent, 
pathogenic or non-pathogenic, is considered serious.  The event may be suspected from 
clinical symptoms or laboratory findings indicating an infection in a patient exposed to a 
Pfizer product.  The terms “suspected transmission” and “transmission” are considered 
synonymous.  These cases are considered unexpected and handled as serious expedited cases
by Pharmacovigilance personnel.  Such cases are also considered for reporting as product 
defects, if appropriate.
Suicidal events
Suicide-related events are considered important medical events that meet the SAE reporting 
requirement.  Suicidal events include worsening suicidal ideation, an interrupted suicide 
attempt, an aborted suicide attempt, preparatory acts or behavior towards making a suicide 
attempt, an actual suicide attempt, or completed suicide. Suicidal events like all SAEs will 
be recorded within 24 hours of the site staff being made aware, not only at the scheduled 
study visits.  At each clinical visit, the study clinician will inquire about new suicidal events 
and complete the post-baseline version of Columbia-Suicide Severity Rating Scale (C-SSRS)
to capture suicidal ideation and suicidal behavior experienced by the patient since his/her last
visit.32,33  To establish a reference baseline, the baseline and screening version of the C-SSRS 
will have been completed as part of the baseline visit.  The C-SSRS will provide a 
standardized, structured framework for completing the Columbia Classification of Suicide 
Assessment (C-CASA) scoring, which is the FDA/European Medicines Agency (EMA)
preferred classification for suicidal events. The PAERS and the HoNOSCA include suicidal 
ideation, suicidal behavior, and harm to others.  If according to pre-defined criteria responses 
on the PAERS and/or the HoNOSCA there is a suggestion that an SAE may have occurred 
but the required SAE assessments have not been completed, the site will be queried regarding 
the accuracy of the SAE reporting requirement. 
Hospitalization
Hospitalization is defined as any initial admission (even if less than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, neurological floor to a
tuberculosis unit). An emergency room visit does not necessarily constitute a hospitalization; 
however, an event leading to an emergency room visit should be assessed for medical 
importance. 
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. 
For example, the following reports of hospitalization without a medical AE are not to be 
reported. 

Social admission (eg, patient has no place to sleep);

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
Administrative admission (eg, for yearly exam);

Optional admission not associated with a precipitating medical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Admission for treatment of a pre-existing condition not associated with the 
development of a new AE or with a worsening of the pre-existing condition (eg, for 
work-up of persistent pre-treatment lab abnormality);

Protocol-specified admission during clinical study (eg, for a procedure required by 
the study protocol).
Scenarios necessitating reporting to Pfizer Safety within 24 hours
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication 
error, overdose, misuse, extravasation, lack of efficacy, and occupational exposure are 
described below.
Exposure during pregnancy
An exposure during pregnancy (EDP) occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or having been 
exposed to (eg, environmental) sertraline, or the female becomes, or is found to be, 
pregnant after discontinuing and/or being exposed to sertraline (maternal exposure).
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male has been exposed, either due to treatment or environmental exposure to 
sertraline prior to or around the time of conception and/or is exposed during the 
partner pregnancy (paternal exposure).
As a general rule, prospective and retrospective exposure during pregnancy reports from any
source are reportable irrespective of the presence of an associated AE and the procedures for
SAE reporting should be followed.
If a study participant or study participant’s partner becomes, or is found to be, pregnant 
during the study participant’s treatment with sertraline, this information must be submitted to 
Pfizer, irrespective of whether an adverse event has occurred using the NIS AEM Report 
Form and the EDP Supplemental Form. 
In addition, the information regarding environmental exposure to sertraline in a pregnant 
woman (eg, a subject reports that she is pregnant and has been exposed to a cytotoxic product 

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by inhalation or spillage) must be submitted using the NIS AEM Report Form and the EDP 
supplemental form. This must be done irrespective of whether an AE has occurred.  
Information submitted should include the anticipated date of delivery (see below for 
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-
up is conducted to obtain information on EDP outcome for all EDP reports with pregnancy 
outcome unknown.  A pregnancy is followed until completion or until pregnancy termination 
(eg, induced abortion) and Pfizer is notified of the outcome.  This information is provided as 
a follow up to the initial EDP report.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (eg, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
procedures for reporting SAEs should be followed.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to investigational product.
Additional information regarding the exposure during pregnancy may be requested.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays).  
In the case of paternal exposure, the study participant will be provided with the Pregnant 
Partner Release of Information Form to deliver to his partner. It must be documented that the 
study participant was given this letter to provide to his partner.
Exposure during breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use. However, if the infant experiences an AE associated with such a 
drug’s administration, the AE is reported together with the exposure during breastfeeding.

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Medication error
A medication error is any unintentional error in the prescribing, dispensing or administration 
of a medicinal product that may cause or lead to inappropriate medication use or patient harm 
while in the control of the health care professional, patient, or consumer.  Such events may 
be related to professional practice, health care products, procedures, and systems including: 
prescribing; order communication; product labeling, packaging, and nomenclature; 
compounding; dispensing; distribution; administration; education; monitoring; and use.  
Medication errors include:

Near misses, involving or not involving a patient directly (eg, inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or 
prescription on the part of the healthcare provider or the patient/consumer);

Confusion with regard to invented name (eg, trade name, brand name).
The investigator must submit the following medication errors to Pfizer, irrespective of the 
presence of an associated AE/SAE:

Medication errors involving patient exposure to the product, whether or not the 
medication error is accompanied by an AE.

Medication errors that do not involve a patient directly (eg, potential medication
errors or near misses).  When a medication error does not involve patient exposure to 
the product the following minimum criteria constitute a medication error report:

An identifiable reporter;

A suspect product;

The event medication error.
Overdose, Misuse, Extravasation
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE.
Lack of Efficacy
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE or the indication for use of the Pfizer 
product.
Occupational Exposure
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the 
investigator, irrespective of the presence of an associated AE/SAE.

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Communication of Issues
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable
Competent Authority in any area of the world, or if the investigator is aware of any new
information which might influence the evaluation of the benefits and risks of sertraline, 
Pfizer should be informed immediately. In addition, the investigator will inform Pfizer 
immediately of any urgent safety measures taken by the investigator to protect the study 
subjects against any immediate hazard, and of any serious breaches of this non-interventional 
study protocol that the investigator becomes aware of. 
9. DATA ANALYSIS/STATISTICAL METHODS
9.1. Power/Sample Size Estimates
In this non-interventional study, 720 subjects will start treatment with sertraline and 180 will 
start with psychotherapy alone.  Statistical testing will be done comparing exposure groups 
determined at the end of the study.  Statistical power in detecting a difference between 
exposure groups is dependent on the type I error, the numbers of subjects in each exposure 
group, and the standardized difference in mean outcome between the groups.
If we consider a 2-tailed type I error equal to 0.05 and 2 groups with 180 subjects each, there 
would be at least 80% power to detect an absolute value of the standardized difference in 
means equal to or greater than 0.3 for any contrast. In other words, the detectable difference
would be 0.3*SD, where SD is the standard deviation of the outcome variable within a group.  
For example, if SD = 1.5, then the detectable difference between means is 0.45 (0.3 x 1.5), 
and if SD = 2.0, it is 0.6 (0.3 x 2.0). Thus, the estimated total sample size required to ensure 
adequate exposure is 720 (4 x 180 sertraline-exposed groups) + 180 (sertraline non-exposed 
comparison group), or 900 subjects total.  If final exposure groups consisted of 
720 sertraline-exposed and 180 psychotherapy-exposed subjects, the comparison of 
sertraline- and psychotherapy-exposed subjects at the specified 4:1 allocation ratio will have 
95% power to detect an absolute value of the standardized difference in means equal to or 
greater than 0.3.
Type I errors for individual comparisons will not take into account multiple testing.
9.2. Analysis Plan
9.2.1. Descriptive Analysis of Primary Outcome Measures
Descriptive summaries will be produced by each visit and treatment exposure for the primary 
outcome measures: Trails B, BRIEF Metacognition Index, BRIEF Behavioral Regulation 
Index, height, weight, and Tanner Scale.  Body Mass Index (BMI) will also be included in 
these descriptive summaries.  
Standardized versions of all of the primary outcome measures, with the exception of the 
Tanner Scale, will be analyzed as well.  The BRIEF, height, weight and BMI outcome 
measures will be sex and age standardized via a Z-score or T-score transformation.  The 
Trails B primary outcome measure will be standardized by age only. For height-adjusted 

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weight data, analysis of BMI standardized for age will be performed using measures 
specified by the Centers for Disease Control and Prevention.  
9.2.2. Marginal Structural Model (MSM) Analysis of Primary Outcome Measures
The main questions of interest are 1) the dose-response relationship between sertraline and 
the primary outcome measures, and 2) the comparison between sertraline-exposed and 
unexposed patients. Change from baseline in Trails B, BRIEF Metacognition Index, BRIEF 
Behavioral Regulation Index, height, weight, BMI and Tanner Scale will be analyzed using 
the repeated measures mixed model via the MSM approach, in order to control for potential 
time-varying confounders and treatment switching during the study. Standardized outcomes 
will be analyzed similarly. In accordance with the MSM approach, adjustment for potential 
time-dependent confounding and treatment switching, as well as adjustment for missing data, 
will be carried out using inverse probability weighting.
1. A dose-response analysis of the relationship between sertraline exposure and each 
outcome will use an empirically derived (accounting for duration and compliance) 
continuous exposure variable, defined as average dose in mg/day, to summarize the 
cumulative sertraline exposure information at each visit over the 3 years of follow-up.
Additional analyses will utilize recent exposure, defined at each visit as average 
sertraline dose (in mg/day) since last visit.  These exposure variables will also be 
a) categorized using pre-specified dose categories, and b) dichotomized; one group 
defined as those with a cumulative exposure greater than zero and the other group 
defined as those not exposed to sertraline. The following areas of interest will be
addressed:
a.
Relationship between visit-specific cumulative exposure (continuous) and the 
outcomes.
b. Relationship between visit-specific cumulative exposure (categorized) and the 
outcomes.
c.
Relationship between visit-specific recent exposure (continuous) and the 
outcomes.
d. Relationship between visit-specific recent exposure (categorized) and the 
outcomes.
2. An analysis of sertraline-exposed and unexposed subjects will compare mean primary 
outcomes at each visit between the Always versus Never Exposed to Sertraline 
exposure categories.  Patients will be categorized according to their actual treatment 
exposure at baseline. Patients’ outcome data will be included in the analysis up to the 
first missed visit or the first visit where they changed treatment as follows: 
a) discontinued sertraline for patients who started on sertraline at baseline, or b) were 
exposed to sertraline for the first time for patients who did not receive sertraline at 
baseline.  Patients who only had baseline visit and no follow-up data will be 
excluded.

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Estimates of the model coefficients and contrasts of interest will be presented with 
95% confidence intervals.  A nominal P-value will be presented. Further details on the
statistical analyses can be found in the study Statistical Analysis Plan (SAP).  
9.3. Methods to Control for Potential Limitations
In observational studies like SPRITES, there is no treatment randomization, and investigators 
assign treatment based on standard of care, eg, their clinical judgment.  Therefore, to 
minimize the effects of potential stable confounders (ie, gender), channeling bias, time-
varying confounders, treatment discontinuation and switches, and/or missing data, a MSM
approach will be utilized.  A MSM analysis is a weighted repeated measures approach using 
treatment as a time-varying covariate.  Weights produce a pseudo-population with a balance 
in both time-invariant and time-varying covariates allowing for causal treatment comparisons 
using standard repeated measures models. Adjustments for missing at random (MAR) or 
missing completely at random (MCAR) can be incorporated directly into the proposed 
models.  
9.4. Sensitivity Analyses
Appropriate sensitivity analyses will be performed to test the robustness of the findings for 
the primary analyses.  Additional details can be found in the statistical analysis plan. 
10. QUALITY CONTROL AND QUALITY ASSURANCE
The DCRI will perform clinical monitoring, including review of the data within the eCRF.  
There will be no source document verification.
See the Clinical Monitoring Plan for additional details.
11. DATA HANDLING AND RECORD KEEPING
Clinical sites will be provided with a printed SPRITES eCRF or the capability to print copies 
of the eCRF, for ease of review and generation of any site-specific source document
templates. SPRITES will use the InFormelectronic data collection (EDC) system to record 
study data obtained from the SPRITES protocol.  Additional data will be collected using the 
Pfizer SAE Form, and the Pfizer Exposure In Utero Supplemental Form, as applicable.  
Investigators will be expected to enter their study data into the eCRF database, a web-based 
system, customized for SPRITES in a timely manner and to report SAEs and Exposure In 
Utero as described in Section 8.
Before initiation of the study, each site will be contacted as to computer availability, 
hardware specifications, and internet connectivity, to evaluate the capacity of the site to use 
this type of data-collection system. The investigator's site staff entering data will receive 
training on the system, after which each person will be issued a unique user identification and 
password.

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For security reasons, and in compliance with regulatory guidelines, it is imperative that only
the person who owns the user identification and password access the system using his or her 
own unique access codes. Access codes are nontransferable. Site personnel who have not 
undergone training may not use the system and will not be issued user identification and 
password until appropriate training is completed.
12. ETHICS
12.1. Institutional Review Board/Independent Ethics Committee
The appropriate institutional review board (IRB)/independent ethics committee (IEC) must 
approve the protocol and parental/guardian permission/subject assent documents, agree to 
monitor the conduct of the study, and agree to review study progress periodically, at intervals 
not to exceed 1 year. The investigator will provide Pfizer, Inc. with documentation that the 
IRB has approved the study before the study may begin.
In addition, the investigator must provide the following documentation to Pfizer, Inc:

IRB annual reapproval of the protocol, per International Conference on 
Harmonisation (ICH), ICH E6, the Good Clinical Practice guideline, and the ethical
principles described therein that have their basis in the Declaration of Helsinki.

IRB approval of revisions to the parental/guardian permission/subject assent 
documents or any amendments to the protocol. Any revisions to the protocol that 
may increase subject risk exposure must be approved before implementation. 
Administrative changes (such as a change in address or phone number) must be sent 
to IRBs/IECs but do not require their approval. The investigator will provide Pfizer, 
Inc. with documentation of all approvals.
12.1.1. Study Approval
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, parental permission/subject assent forms, and other relevant 
documents, if applicable, from the IRB/IEC. All correspondence with the IRB/IEC should be 
retained in the investigator file. Copies of IRB/IEC approvals should be forwarded to Pfizer, 
Inc.
12.1.2. Amendments to the Protocol
Once the protocol has been approved by the local site IRB, the site investigators will not 
modify it. The site investigators will be notified in writing of any amendments to the 
protocol and/or the parental/guardian permission or subject assent form. The site 
investigators must obtain permission in writing from the IRB before implementing protocol 
amendments or parental/guardian permission or subject assent form changes. 
The only circumstance in which an amendment may be initiated before IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In 
that event, the investigator must notify the IRB/IEC and Pfizer, Inc. in writing within 
5 working days after the implementation.

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The principal investigator or his or her study staff must notify the local IRB when the study
is closed and provide a final report within 1 year of the last subject’s completion of the study. 
12.2. Ethical Conduct of the Study
The study will be conducted in compliance with 45CFR46, 21CFR50, 21CFR56, 21CFR312, 
21CFR812, and 45CFR164.508-514, and in compliance with the Guidelines of the 
International Conference on Harmonization (ICH), to the extent required by the U.S. Food 
and Drug Administration. 
By signing this protocol, the investigator agrees to conduct the study in compliance with the 
protocol, applicable standard operating procedures and/or guidelines, the ICH guidelines and 
the ethical principles described therein that have their basis in the Declaration of Helsinki, 
and all applicable federal, state, and local laws, rules, and regulations relating to the conduct
of the clinical study.
12.3. Subject Information and parental/guardian permission/assent
All parties will ensure protection of subject personal data and will not include subject names 
on any sponsor forms, reports, publications, or in any other disclosures. In case of data 
transfer, Pfizer, Inc. will maintain high standards of confidentiality and protection of subject 
personal data. The parental/guardian permission/subject assent forms must be agreed to by 
Pfizer, Inc. and the IRB/IEC and must be in compliance with local regulatory requirements 
and legal requirements. The investigator must ensure that each study subject and his/her 
parents/guardian are fully informed about the nature and objectives of the study and possible 
risks associated with participation. The investigator, or a person designated by the 
investigator, will obtain written parental/guardian permission and assent from each subject, 
per local IRB requirements before any study-specific activity is performed. The 
parental/guardian permission and assent forms used in this study, and any changes made 
during the course of the study, must be prospectively approved by both the IRB/IEC and 
Pfizer, Inc. before use. The investigator will retain the original of each subject's signed 
assent and parental/guardian permission forms. Subjects will provide written assent as 
required by the local site IRB.
12.3.1. Subject Information
Each subject will be identified by a subject identification number assigned in the eCRF. 
Each subject ID will be an anonymous alphanumeric code. A subset of identifying 
information will be collected to ensure the accuracy and validity of the data and to achieve 
the scientific aims of the study. Specifically, the subject’s age will be collected since this is 
an important predictor of differential response to medication. Subject initials will be 
collected and displayed to clinicians entering subject data into the system. This is to ensure 
that when a subject number is selected, the clinician can confirm that he or she is entering 
data for the correct subject. Other identifying information, such as the subject’s name, Social 
Security number, or e-mail address will not be recorded on the CRF pages or within the 
database system.

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12.3.2. Parental/guardian permission/assent
The investigator has both ethical and legal responsibility to ensure that each subject being 
considered for inclusion in this study is given a full explanation of the study. Written 
parental/guardian permission and assent, per local IRB requirements will be obtained for all 
subjects before any study-related assessments or procedures are performed. 
Written parental/guardian permission/assent will be documented on forms approved by the 
same IRB responsible for approval of this protocol. The forms will conform to ICH
guidelines and to the institutional requirements for parental/guardian permission/assent and 
applicable regulations. The investigator agrees to obtain approval from Pfizer, Inc. for any 
parental/guardian permission/assent form intended for use in the study, before submission for 
IRB approval.
The parental/guardian permission/assent forms will be reviewed with the prospective study 
subject and his or her parent, and the investigator or qualified designee will be available to 
answer questions regarding procedures, risks, and alternatives. 
Once the appropriate essential information has been provided to the subject and fully 
explained by the investigators or qualified designee, and it is felt that the subject and parent 
understand the implications of participating, the subject, parent and the investigator or 
designee will sign and date the IRB-approved parental/guardian permission/assent forms. 
The subject will receive a copy of the signed forms. The original signed and dated forms will 
be kept in the site’s regulatory file. Documentation of the parental/guardian 
permission/assent process for participation in this trial will be noted in the subject’s medical 
record. 
If the subject is illiterate, an additional impartial witness may be required to participate in the 
parental/guardian permission/assent process per local IRB requirements.
The subject or his or her parent will be informed in a timely manner if new information 
becomes available that may be relevant to the subject’s willingness to continue participation 
in the trial. The communication of this information to the subject will be documented.
12.4. Confidentiality
Subjects will be assigned a unique subject ID by which they will be identified; the key (the 
patient-identifying information) will be held securely at the local enrolling site and will not 
be transmitted to the study sponsor or to data management. However, when reporting SAEs, 
the site will include the unique ID, gender, and date of birth on the AE form. Investigators 
will be provided with electronic access to CRFs for data submission as required for each 
research subject and any other forms as necessary. The investigator and/or institution will:

Maintain a study file for each subject, to include at a minimum the signed
parental/guardian permission and assent (if applicable).

Maintain current IRB approval and keep a regulatory file with copies of all IRB 
correspondence.

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
Submit SAE forms immediately and other data according to the data schedule, to 
allow for reporting of SAEs to the FDA and other regulatory authorities if necessary, 
as well as safety analyses.
Safety data will be forwarded to the EMA and other regulatory bodies by Pfizer, Inc., per 
relevant regulations.  No other individual subject will be identified in study reports or 
publications. Records may be reviewed in order to meet federal or state regulations. Upon 
the request of authorized personnel from Pfizer, Inc., its designees, or the FDA, or regulatory 
authorities from other countries, the investigator will make available for inspection source 
documents, ie, records of each subject who participates in this study. This information will 
be treated as confidential and all efforts will be made to avoid further disclosures.
All research records will be treated as confidential and will be kept in locked files. Access 
will be allowed only to members of the research team, institutional staff, and regulatory 
agencies as mandated by law. All records will be kept confidential to the extent permitted by 
law.  Information linking subjects to their research data will be kept in locked files at study 
sites. In reporting the results of this study, privacy will be protected by reporting group
results. Research analytic databases will be fully unlinked and de-identified in compliance 
with the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule and the 
Common Rule, and access to research databases for additional analyses will be in accordance 
with the agreement with Pfizer, Inc.
12.5. Authorization for Use and Disclosure of Protected Health Information (Health 
Insurance Portability and Accountability Act)
An authorization for use and disclosure of protected health information (PHI) under the 
Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule (45 CFR § 
164.102 et seq) will be obtained from every trial subject prior to, or at the time of, 
enrollment. It will be presented to, and signed by, the subject at the same time as 
parental/guardian permission/assent. The investigator is responsible for obtaining subjects’ 
and parent’s authorizations and signatures, and for explaining the elements of the HIPAA 
Authorization form if necessary.
HIPAA authorization may either be a separate form or included in the parental/guardian 
permission/assent, dependent upon local requirements.  If a separate HIPAA document is 
signed, the investigator will append 1 signed original of each executed HIPAA authorization
to the trial subject’s signed parental/guardian permission/assent and file it in the site’s 
regulatory file. If a second copy of the signed parental/guardian permission/assent is filed in 
the subject’s medical records, an additional copy of the signed HIPAA authorization form 
will be appended. Subjects will be given the other signed duplicate for their personal 
records.

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The HIPAA authorization form will contain all elements required under the HIPAA Privacy 
Rule. By law, site IRB approval of the sponsor-provided authorization form for use in this 
study is not required, and no such approval will be sought or requested. However, Pfizer, 
Inc., upon request, will provide advance copies of its HIPAA authorization form to the 
investigator or the site’s privacy board or privacy official and will work with the site to 
eliminate any concerns.
The investigator or the site will promptly inform Pfizer, Inc. of any restrictions on the use or 
disclosure of PHI of any subject to which the site or the investigator have agreed under the 
Privacy Rule.  The investigator or the site will also promptly inform Pfizer, Inc. of any 
written revocation of any subject’s HIPAA authorization.
12.6. Cost to Subjects
There will be no additional costs to the subject for participating in this study other than the 
additional time required to complete the questionnaires. No treatments will be provided as 
part of the study, and non-study treatment costs will be paid through whatever mechanism 
the subject or his or her parent normally uses for medical care (insurance, health maintenance 
organization, government program, self-pay, etc.). 
13. DEFINITION OF END OF STUDY
The end of study is defined as last subject’s last visit at the time of study termination.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision,
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Pfizer, Inc.  If 
a study is prematurely terminated or discontinued, Pfizer, Inc. will promptly notify the
investigator. After notification, the investigator must contact all participating subjects within 
3 months. As directed by Pfizer, Inc., all study materials must be collected and all CRFs 
completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
Publication of study results is discussed in the Clinical Study Agreement.
The DCRI Coordinating Investigators working with the sponsor will be primarily responsible 
for creation, review, and submission of the primary publications and presentations relating to 
the major aspects of the study and approved ancillary analyses within a timely fashion after 
completion of the study. 
The manuscript containing the overall study results will be distributed to Pfizer, Inc. for 
review before submission to a peer-reviewed journal, but the final contents will be at the 
discretion of the principal investigator. Any other manuscripts containing these data,
including abstracts, will be distributed to Pfizer, Inc. before submission with a reasonable 
period for review. Submitted publications will conform to international standards for 
biomedical manuscripts, including those regarding authorship.

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16. STUDY GOVERNANCE
SPRITES will be subject to IRB review and monitoring. 
No study governance structure (ie, scientific advisory board or data and safety monitoring 
board) will be put in place, given the aims and nature of this study. 

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17. REFERENCES
1.
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P P D
P P D