Fluarix/ FluLaval/ Fluarix Quadrivalent/ FluLaval Quadrivalent Pregnancy Registry: a Prospective, Exploratory, Cohort Study to Detect and Describe Abnormal Pregnancy Outcomes in Women Intentionally or Unintentionally Vaccinated With Fluarix or Fluarix Quadrivalent or FluLaval or FluLaval Quadrivalent During Pregnancy or Within 28 Days Preceding Conception.
Conditions: Influenza
Sponsor: GlaxoSmithKline

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Study Protocol 
Sponsor: 
GlaxoSmithKline Biologicals 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
1. 
PASS INFORMATION 
Title 
Fluarix®/ FluLaval®/ Fluarix® Quadrivalent/ 
FluLaval® Quadrivalent Pregnancy Registry: a 
prospective, exploratory, cohort study to detect 
and describe abnormal pregnancy outcomes in 
women intentionally or unintentionally 
vaccinated with Fluarix® or Fluarix® 
Quadrivalent or FluLaval® or FluLaval® 
Quadrivalent during pregnancy or within 28 
days preceding conception. 
Protocol version identifier 
201476 (EPI-FLU-039 VS US PR) 
Date of last version of the 
protocol  
Final Version 1: 13 May 2014 
Amendment 1 Final: 27 October 2017 
EU PAS Register No: 
Not applicable 
Active substance 
J07BB02, Influenza Virus Vaccines 
Medicinal products: 
Fluarix®, FluLaval®, Fluarix® Quadrivalent, 
FluLaval® Quadrivalent, Inactivated Influenza 
Virus Vaccines 
Product reference: 
Not applicable 
Procedure number: 
Not applicable 
Marketing Authorization 
Holder 
GlaxoSmithKline Biologicals 
Rue de l’Institut 89 
1330 Rixensart, Belgium 
Joint PASS 
No 
Research question and 
objectives 
Co-primary objectives 
• 
To describe the characteristics of 
prospectively reported pregnancies 
(women vaccinated with Fluarix or 
FluLaval or Fluarix Quadrivalent or 
FluLaval Quadrivalent during pregnancy or 

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within 28 days preceding conception) with 
abnormal pregnancy outcomes. 
• 
To assess the proportion of prospectively 
reported pregnancies (women vaccinated 
with Fluarix or FluLaval or Fluarix 
Quadrivalent or FluLaval Quadrivalent 
during pregnancy or within 28 days 
preceding conception) with abnormal 
pregnancy outcomes. 
Country of study 
United States 
Authors (Amended on 27 
October 2017) 
Coordinating author: 
• 
, XPE Pharma & Science, 
contractor for GSK Biologicals 
GSK contributors: 
• 
, Director, Safety Evaluation & 
Risk Management, Vaccine Clinical Safety 
and Pharmacovigilance 
• 
, Director, Safety Evaluation 
& Risk Management, Vaccine Clinical 
Safety and Pharmacovigilance 
• 
, Director and Head, Clinical 
Safety Sciences, Vaccine Clinical Safety and 
Pharmacovigilance 
• 
, VP, Head Vaccine 
Clinical Safety and Pharmacovigilance 
• 
, Director, Global Clinical R&D 
• 
, Senior Manager, Vaccine 
Value & Health Science Epidemiology 
• 
, Director, Vaccine Value & 
Health Science Epidemiology 
• 
, Senior Manager, Regulatory 
Affairs 
• 
, Safety Scientist, 
Safety Evaluation & Risk Management, 
Vaccine Clinical Safety and 
Pharmacovigilance 
• 
, Head, Safety Evaluation & 
Risk Management, Vaccine Clinical Safety 
and Pharmacovigilance 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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• 
, Clinical and Epidemiology 
Project Lead, Influenza Vaccines 
• 
, North America Regulatory 
Affairs 
• 
, Manager, Case 
Management Group (CMG) 
• 
, Clinical Safety Associate 
• 
, Director, CMG 
• 
, Study Delivery 
Lead 
• 
, Senior Epidemiology 
Expert, US RDC 
• 
, Lead Epidemiologist 
2. 
MARKETING AUTHORIZATION HOLDER 
Marketing authorization holder 
GlaxoSmithKline Biologicals 
Rue de l’Institut 89, 1330 Rixensart, Belgium 
© [2014-2017] GSK group of companies or its licensor 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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TABLE OF CONTENTS 
PAGE 
1. 
PASS INFORMATION .............................................................................................. 1 
2. 
MARKETING AUTHORIZATION HOLDER .............................................................. 3 
LIST OF ABBREVIATIONS ............................................................................................. 8 
3. 
RESPONSIBLE PARTIES ........................................................................................ 9 
4. 
ABSTRACT .............................................................................................................. 9 
5. 
AMENDMENTS AND UPDATES ............................................................................ 13 
6. 
MILESTONES (AMENDED ON 27 OCTOBER 2017) ............................................. 13 
7. 
RATIONALE AND BACKGROUND ........................................................................ 14 
7.1. 
Background ................................................................................................ 14 
7.1.1. 
Trivalent influenza vaccines ......................................................... 14 
7.1.1.1. 
Animal studies ............................................................ 15 
7.1.1.2. 
Post marketing exposure in pregnant women ............. 16 
7.1.2. 
Quadrivalent influenza vaccines .................................................. 17 
7.1.2.1. 
Animal studies ............................................................ 17 
7.1.2.2. 
Post marketing exposure in pregnant women ............. 18 
7.1.2.3. 
GSK sIIVs .................................................................. 18 
7.1.3. 
Medical conditions for use (Amended on 27 October 2017) ......... 19 
7.1.4. 
Characteristics of exposure.......................................................... 19 
7.1.5. 
Potential benefits of product......................................................... 19 
7.2. 
Rationale .................................................................................................... 19 
8. 
RESEARCH QUESTION AND OBJECTIVES ........................................................ 20 
8.1. 
Co-primary objectives ................................................................................. 20 
9. 
RESEARCH METHODS ......................................................................................... 20 
9.1. 
Study design ............................................................................................... 20 
9.1.1. 
Overview (Amended on 27 October 2017) ................................... 20 
9.1.2. 
Rationale for study design ........................................................... 21 
9.2. 
Setting ........................................................................................................ 22 
9.2.1. 
Study population .......................................................................... 22 
9.2.1.1. 
Patient population (Amended on 27 October 
2017) ......................................................................... 22 
9.2.1.2. 
Potential annual exposure (Amended on 27 
October 2017) ........................................................... 22 
9.2.2. 
Patient recruitment (Amended on 27 October 2017) .................. 22 
9.2.3. 
Selection of a comparison group ............................................... 22 
9.2.4. 
Study period ................................................................................ 23 
9.2.5. 
Inclusion criteria (Amended on 27 October 2017) ...................... 23 
9.2.6. 
Exclusion criterion ........................................................................ 23 
9.3. 
Variables..................................................................................................... 23 
9.3.1. 
Primary endpoint .......................................................................... 23 
9.3.2. 
Data to be collected (Amended on 27 October 2017) ................ 23 

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9.3.2.1. 
Questionnaire for initial data collection 
(Amended on 27 October 2017) ............................... 24 
9.3.2.2. 
Questionnaire for pregnancy outcome data 
collection (Amended on 27 October 2017) ............... 24 
9.3.2.3. 
Questionnaire for infant data collection ....................... 25 
9.4. 
Data sources (Amended on 27 October 2017) ......................................... 25 
9.5. 
Study size ................................................................................................... 25 
9.6. 
Data management ...................................................................................... 25 
9.6.1. 
Data collection (Amended on 27 October 2017) ........................ 25 
9.6.2. 
Processing of reports (Amended on 27 October 2017) .............. 26 
9.6.2.1. 
Solicitation of outcomes (Amended on 27 
October 2017) ........................................................... 27 
9.6.2.2. 
Classification of outcomes .......................................... 27 
9.7. 
Data analysis (Amended on 27 October 2017) ......................................... 28 
9.8. 
Quality control ............................................................................................. 29 
9.9. 
Limitations of the research methods ........................................................... 30 
10. PROTECTION OF HUMAN SUBJECTS ................................................................ 30 
10.1. 
Regulatory and ethical considerations, including the informed 
consent process.......................................................................................... 30 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE 
REACTIONS .......................................................................................................... 31 
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY 
RESULTS (AMENDED ON 27 OCTOBER 2017) ................................................ 31 
13. REFERENCES ....................................................................................................... 31 
 

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LIST OF TABLES 
PAGE 
Table 1 
Current Pregnancy Registry Protocols being conducted for 
Fluarix, FluLaval, Fluarix Quadrivalent and FluLaval Quadrivalent ......... 14 
Table 2 
Outcomes of pregnancy exposed to Fluarix ........................................... 16 
Table 3 
Outcomes of pregnancy exposed to FluLaval ..................................... 17 
Table 4 
Outcomes of pregnancy exposed to Fluarix Quadrivalent .................. 18 
Table 5 
Year of initial US approval for GSK sIIVs ............................................... 19 
 

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LIST OF ANNEXES 
PAGE 
ANNEX 1 
List of stand-alone documents ................................................................ 34 
ANNEX 2 
ENCePP Checklist for study protocols ................................................... 35 
ANNEX 3 
Glossary of terms ................................................................................... 36 
ANNEX 4 
Amendments and administrative changes to the protocol ....................... 38 
ANNEX 5 
Trademarks ............................................................................................ 57 
ANNEX 6 
Protocol Amendment 1 sponsor signatory approval ............................... 58 
 

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LIST OF ABBREVIATIONS 
ACIP 
Advisory Committee on Immunization Practices 
AE 
Adverse Event 
BLA 
Biologics License Application 
CBER 
Center for Biologics Evaluation and Research 
CDC 
Centers for Disease Control and Prevention 
EDD 
Estimated Date of Delivery 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GSK 
GlaxoSmithKline 
HA 
Hemagglutinin 
HCP 
Healthcare Professional 
ICH 
International Conference on Harmonization 
IM 
Intramuscular 
IND 
Investigational New Drug 
LMP 
Last Menstrual Period 
MACDP 
Metropolitan Atlanta Congenital Defects Program 
PASS 
Post Authorization Safety Study 
PI 
Prescribing Information 
sIIV(s) 
seasonal Inactivated Influenza Vaccine(s) 
US 
United States 
VCSP 
Vaccine Clinical Safety and Pharmacovigilance 

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3. 
RESPONSIBLE PARTIES 
GlaxoSmithKline (GSK) Biologicals has the overall responsibility for the conduct of the 
study. 
4. 
ABSTRACT 
Title 
Fluarix®/ FluLaval®/ Fluarix® Quadrivalent/ FluLaval® 
Quadrivalent Pregnancy Registry: an exploratory prospective, 
cohort study to detect and describe abnormal pregnancy 
outcomes in women intentionally or unintentionally vaccinated 
with Fluarix® or Fluarix® Quadrivalent or FluLaval® or 
FluLaval® Quadrivalent during pregnancy or within 28 days 
preceding conception. 
201476 (EPI-FLU-039 VS US PR), Amendment 1 Final: 27 
October 2017 
Main author 
, Director, Safety Evaluation & Risk Management, 
Vaccine Clinical Safety and Pharmacovigilance, GSK 
Biologicals 
Rationale and 
background 
The four seasonal Inactivated Influenza Vaccines Fluarix, 
FluLaval, Fluarix Quadrivalent and FluLaval Quadrivalent 
(collectively referred to as GSK seasonal Inactivated Influenza 
Vaccines [GSK sIIVs]) are approved in the United States (US) 
for prevention of disease caused by influenza A 
subtype viruses and type B viruses contained in the 
vaccine in persons 3 years of age and older. 
Pregnant women may inadvertently be vaccinated with GSK 
sIIVs during the first trimester, before pregnancy is known. In 
general, the women are closely monitored throughout the 
remainder of the pregnancy. 
The purpose of this pregnancy registry study is to detect and 
describe abnormal pregnancy outcomes in women intentionally 
or unintentionally vaccinated with GSK sIIVs. The 
combination of the large number of women who are of 
reproductive capacity in the indicated age range for 
vaccination with these vaccines and the lack of data 
concerning vaccination with GSK sIIVs during pregnancy 
makes such a Registry an important component of the 
ongoing program to assess the safety of these four vaccines. 
The intent of the Registry is to prospectively collect data such 
as vaccination with GSK sIIVs during pregnancy or within 28 
days preceding conception, potential confounding factors (such 
PPD

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as exposure to other medications) and information related to 
the outcome of the pregnancy. 
Research question 
and objectives 
Co-primary objectives 
• 
To describe the characteristics of prospectively reported 
pregnancies (women vaccinated with Fluarix or FluLaval 
or Fluarix Quadrivalent or FluLaval Quadrivalent during 
pregnancy or within 28 days preceding conception) with 
abnormal pregnancy outcomes. 
• 
To assess the proportion of prospectively reported 
pregnancies (women vaccinated with Fluarix or FluLaval 
or Fluarix Quadrivalent or FluLaval Quadrivalent during 
pregnancy or within 28 days preceding conception) with 
abnormal pregnancy outcomes. 
Study design 
(Amended on 27 
October 2017) 
• 
This study is a transition of existing ongoing pregnancy 
registries for Fluarix, FluLaval and Fluarix 
Quadrivalent and an ongoing PASS for FluLaval 
Quadrivalent into a combined PASS for these four GSK 
sIIVs. 
• 
This is an exploratory prospective, observational, cohort 
study. The GSK sIIVs pregnancy registry study requires 
voluntary, prospective* reporting of eligible pregnancies 
by patients and healthcare professionals (HCPs). Data such 
as vaccination with GSK sIIVs during pregnancy or within 
28 days preceding conception, potential confounding factors 
(such as exposure to other medications) and information 
related to the outcome of the pregnancy will be collected 
prospectively. 
*Some pregnancy exposures may be reported when the 
outcome is unknown (prospective reports). 
Some pregnancy exposures may be reported after 
pregnancy outcome has been identified (retrospective 
reports). The Registry will capture retrospective reports, 
but these reports will not be included in the analyses of 
prospective reports. 
• 
This study is a post-marketing commitment in the US. 
• 
Study population: pregnant women, vaccinated with GSK 
sIIVs during pregnancy or within 28 days preceding 
conception volunteering to take part in the study. 
• 
Type of study: self-contained. 
• 
Data collection: Initial and follow-up data will be 
collected using questionnaires (Initial notification form, 
Pregnancy outcome form and 6 and 12-month post-

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delivery follow-up form). Initial data can be collected 
from pregnant subjects, their healthcare providers or 
both. Follow-up of cases is performed within 2 months 
of the estimated date of delivery (EDD) to ascertain 
outcome and approximately 6 months and 12 months after 
the EDD (for all live births for whom the contact details of 
their HCP will be available) to ascertain the presence of 
birth defects not diagnosed before. Follow-up 
questionnaires can only be completed by healthcare 
providers and/or HCP staff. 
• 
After transition of the ongoing pregnancy registries into 
one combined PASS for GSK sIIVs, data will be collected 
for a minimum of 5 years starting Q2 2014 
Population, 
including the 
setting and study 
population 
(Amended on 27 
October 2017) 
In the US, GSK sIIVs are indicated for prevention of disease 
caused by influenza A subtype viruses and type B viruses 
contained in the vaccine. Currently, GSK sIIVs are 
approved for use in persons 3 years of age and older or 6 
months of age and older, depending on the vaccine. 
Size of the potential “at-risk” population 
In the year 2012, the fertility rate in the US was 63.2 births 
per 1000 women aged 15-44 years and there were 3.96 
million births [CDC, 2012]. 
Number of pregnant vaccinees 
Although the number of pregnant women who will be 
vaccinated with GSK IIVs through this registry is impossible to 
predict, experiences with other vaccine pregnancy registries 
indicate that it is likely that fewer than 100 pregnancies per 
year will be registered for each of the vaccines. 
Variables 
Primary endpoint 
Occurrence of abnormal pregnancy outcomes in women 
intentionally or unintentionally vaccinated with GSK sIIVs 
during pregnancy or within 28 days preceding conception. 
Data sources 
(Amended on 27 
October 2017) 
Reporting of vaccine-exposed pregnancies to the Registry is 
voluntary. Registration can be initiated from a HCP or from 
a consumer. Permission from consumers is requested to 
obtain confirmation and follow-up from their HCP, as well 
as follow-up from the HCP of their infant. A toll-free 
telephone number for reporting adverse events (AEs) and 
vaccine-exposed pregnancies to the Registry are listed in the 
product information leaflet and on the GSK Registry website. 

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Retrospective post-marketing reports and relevant scientific 
publications are potential sources of additional information. 
Study size 
No minimum sample size is required for this descriptive, 
exploratory study. 
Please refer to Abstract Section “Study population” above 
for the size of the potential “at-risk” population and the 
number of pregnant vaccinees. 
Data analysis 
(Amended on 27 
October 2017) 
Pregnancy outcomes include spontaneous abortion (pregnancy 
loss before 22 weeks gestation), fetal deaths/stillbirths (loss 
at or after 22 weeks gestation), elective/therapeutic abortions 
and live births. The presence or absence of birth defects or 
other abnormalities is evaluated within each of the preceding 
outcome categories. 
Pregnancy outcomes are stratified by the trimester of 
exposure, with an additional stratum for preconception 
exposure with no subsequent administration of vaccine during 
pregnancy. Reports of multiple exposures during a pregnancy 
are classified by the earliest trimester of exposure. The 
calculations of risk for birth defects are made by dividing the 
number of infants with birth defects by the total number of 
infants with and without birth defects. An exact 95% 
confidence interval is calculated using standard statistical 
software. The outcomes of the study will be assessed against 
known rates from an external reference group for the likelihood 
of a safety signal warranting further investigation. 
Spontaneous abortions without birth defects are excluded from 
the risk calculations. 
All defects regardless of trimester of vaccine exposure will be 
included in the periodic summary reports of this Registry and 
stratified by trimester of exposure. 
A section of each periodic summary report, separate from the 
analysis of prospective reports, will describe all abnormal 
outcomes of retrospectively reported cases. 
Milestones 
(Amended on 27 
October 2017) 
Summary reports with cumulative analyses will be written 
annually and submitted with the Periodic Benefit-Risk 
Evaluation Report (PBRER) for each GSK sIIV. A final 
report will be written and submitted approximately18 months 
after the last annual report.  
After submission of the final report, GSK will continue the 
Registry pending Center for Biologics Evaluation and 

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Research (CBER) review of the report and determination 
whether the Registry can be discontinued. 
References 
Centers for Disease Control and Prevention (CDC). Recent 
Trends in Births and Fertility Rates Through December 2012. 
Available at 
http://www.cdc.gov/nchs/data/hestat/births_fertility_december_2
012/births_fertility_december_2012.htm 
Accessed 29 August 2013. 
5. 
AMENDMENTS AND UPDATES 
The summary of the amendment is provided in ANNEX 4 
 
6. 
MILESTONES (AMENDED ON 27 OCTOBER 2017) 
Milestone 
Planned date a 
Start of data collection 
01 June 2014 b 
End of data collection 
31 May 2019 c 
Annual report 1 (2014-2015 influenza season) 
10 February 2016 
Annual report 2 (2015-2016 influenza season) 
10 February 2017 
Annual report 3 (2016-2017 influenza season) 
10 February 2018 
Annual report 4 (2017-2018 influenza season) 
10 February 2019 
Annual report 5 (2018-2019 influenza season) 
10 February 2020 
Final report 
August 2021 
a The Fluarix and FluLaval Registries were originally initiated on 02 Sep 2011. The Fluarix Quadrivalent and 
FluLaval Quadrivalent Registries were originally initiated on 30 Aug 2013 and 30 Nov 2013, respectively. In 
2014. the ongoing Registries were combined and converted into a PASS. GSK plans to continue the Registry 
for a minimum of 5 years, starting Q2 2014. 
b Women vaccinated with GSK sIIVs during pregnancy or within 28 days preceding conception, reported before 
the planned date of start of data collection (01 June 2014) but for which the pregnancy outcome is not yet 
known, may be enrolled retroactively in the Registry. 
c After submission of the final report, GSK will continue the Registry pending Center for Biologics Evaluation and 
Research (CBER) review of the report and determination whether the Registry can be discontinued. 

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7. 
RATIONALE AND BACKGROUND 
7.1. 
Background 
Both Fluarix and Fluarix Quadrivalent vaccines are manufactured by GSK Biologicals, in 
Dresden, Germany. 
Both FluLaval and FluLaval Quadrivalent vaccines are manufactured by ID Biomedical 
Corporation of Quebec, a subsidiary of GSK; in Quebec City, Canada. 
GSK currently has 4 Pregnancy Registry protocols that have been submitted to 
Investigational New Drug (IND) and Biologics License Applications (BLAs). These were 
submitted either as a postmarking commitment or as voluntary pharmacovigilance 
activities in a Risk Management Plan for the GSK sIIVs. See Table 1 for information on 
these registries. 
Table 1 
Current Pregnancy Registry Protocols being conducted for Fluarix, 
FluLaval, Fluarix Quadrivalent and FluLaval Quadrivalent 
Product Name 
File Number 
Submission Date of 
Pregnancy Registry 
Protocol 
Registry Starting 
Date 
Fluarix 
125127 
31 August 2010 (Sequence 
No. 0065) 
02 September 
2011 
FluLaval 
125163/181 
10 August 2010 (Sequence 
No. 0027) 
02 September 
2011 
Fluarix 
Quadrivalent 
125127 
BB-IND 114473 
15 April 2013 (Sequence 
No. 0181) 
13 June 2013 (Sequence 
No. 0036) 
30 August 2013 
FluLaval 
Quadrivalent 
125163 
BB-IND 14466 
29 October 2013 (Sequence 
No. 0157) 
28 October 2013 (Sequence 
No.0032) 
30 November 2013 
7.1.1. 
Trivalent influenza vaccines 
Fluarix and FluLaval are both split virion, inactivated influenza vaccines consisting of 
equal amounts of three monovalent viral antigen bulks prepared from influenza strains 
A/H1N1, A/H3N2 and one B strain. One dose of the split inactivated vaccine contains 15 
μg hemagglutinin (HA) for each of the three influenza virus strains, for a total of 45 μg 
HA/0.5 mL dose. 

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7.1.1.1. 
Animal studies 
Animal reproduction studies were performed in female rats using 0.1 mL (approximately 
56 times the human dose based on average weight) of Fluarix administered 28 days 
before mating and on Days 6, 8, 11 and 15 of gestation. There were no adverse effects on 
mating performance or fertility of the female rats, and no adverse effects on embryo/fetal 
survival, growth or development, or the pre- or post-natal survival, growth or 
development of the offspring up to 25 days of age [Fluarix Prescribing Information (PI), 
2013]. 
In a reproductive and developmental toxicity study, the effects of FluLaval on embryo-
fetal and pre-weaning development were evaluated in pregnant rats. Animals were 
administered FluLaval by intramuscular injection, once prior to gestation and on 
gestation days 6, 8, 11, and 15 during the period of organogenesis, at a dose of 0.1 
mL/rat/occasion (approximately 40-fold excess relative to the projected human dose on a 
body weight basis). No adverse effects on mating, female fertility, pregnancy, parturition, 
lactation parameters, and embryo-fetal or pre-weaning development were observed. 
There were no vaccine-related fetal malformations or other evidence of teratogenesis 
[FluLaval PI, 2013]. 

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7.1.1.2. 
Post marketing exposure in pregnant women 
Fluarix: 
Overall, as of 31 May 2017, GSK had received 236 reports of exposure to Fluarix during 
pregnancy since its launch on 04 July 1991. The outcomes of the 236 pregnancies are 
summarized in Table 2. 
Table 2 
Outcomes of pregnancy exposed to Fluarix 
Outcome 
Number of Cases  
since launch (n) 
Live infant, no apparent congenital anomaly * 
52 
Live infant with congenital anomaly 
1 
Elective termination, no apparent congenital anomaly * 
0 
Elective termination with congenital anomaly 
1 
Spontaneous abortion, no apparent congenital anomaly * 
8 
Spontaneous abortion with congenital anomaly 
1 
Stillbirth, no apparent congenital anomaly * 
0 
Stillbirth with congenital anomaly 
0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing, lost to follow-up or unknown 
173 
Total 
236 
* Pregnancy outcome categories stating no apparent congenital anomaly include outcomes where it is unknown 
whether a congenital anomaly occurred. 
FluLaval: 
Overall, as of 31 May 2017, GSK had received 130 reports of exposure to FluLaval 
during pregnancy since launch on 18 December 1992. The outcomes of the 130 
pregnancies are summarized in Table 3. 

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Table 3 
Outcomes of pregnancy exposed to FluLaval 
Outcome 
Number of Cases  
since launch 
Live Infant, no apparent congenital anomaly * 
46 
Live infant with congenital anomaly 
1 
Elective termination, no apparent congenital anomaly * 
0 
Elective termination with congenital anomaly 
0 
Spontaneous abortion, no apparent congenital anomaly * 
3 
Spontaneous abortion with congenital anomaly 
0 
Stillbirth, no apparent congenital anomaly * 
0 
Stillbirth with congenital anomaly 
0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing / Unknown / Lost to Follow-up 
80 
Total 
130 
* Pregnancy outcome categories stating no apparent congenital anomaly include outcomes where it is unknown 
whether a congenital anomaly occurred. 
7.1.2. 
Quadrivalent influenza vaccines 
Fluarix Quadrivalent and FluLaval Quadrivalent are split virion, inactivated influenza 
vaccines consisting of equal amounts of four monovalent viral antigen bulks prepared 
from influenza strains A/H1N1, A/H3N2 and two B strains (one B/Yamagata lineage and 
one B/Victoria lineage). One dose of the split inactivated vaccine contains 15 μg HA for 
each of the four influenza virus strains, for a total of 60 μg HA/0.5 mL dose. 
7.1.2.1. 
Animal studies 
Reproductive and developmental toxicity of Fluarix Quadrivalent and FluLaval 
Quadrivalent has been studied in female rats at doses approximately 80 times the human 
dose (on a mg/kg basis) and no evidence of impaired female fertility or harm to the fetus 
was observed. 
In reproductive and developmental toxicity studies, the effect of Fluarix Quadrivalent 
and FluLaval Quadrivalent on embryo-fetal and pre-weaning development was evaluated 
in rats. Animals were administered Fluarix Quadrivalent or FluLaval Quadrivalent by 
intramuscular (IM) injection twice prior to gestation, during the period of organogenesis 
(gestation days 3, 8, 11 and 15) and during lactation (day 7), 0.2 mL/rat/occasion 
(approximately 80-fold excess relative to the projected human dose on a body weight 
basis). No adverse effects on embryo-fetal or peri- and post-natal development, no 

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maternal toxicity and no impact on F0 female clinical condition, food consumption, body 
weight, mating performance, fertility or ability to produce a live litter were observed 
during these studies [Fluarix Quadrivalent PI, 2013; FluLaval Quadrivalent PI, 2013]. 
7.1.2.2. 
Post marketing exposure in pregnant women 
Fluarix Quadrivalent: 
Overall, as of 31 May 2017, GSK had received 64 reports of exposure to Fluarix 
Quadrivalent during pregnancy since launch on 5 August 2013. The outcomes of the 64 
pregnancies are summarized in Table 4. 
Table 4 
Outcomes of pregnancy exposed to Fluarix Quadrivalent 
Outcome 
Number of Cases  
since launch (n) 
Live infant, no apparent congenital anomaly * 
15 
Live infant with congenital anomaly 
0 
Elective termination, no apparent congenital anomaly * 
0 
Elective termination with congenital anomaly 
0 
Spontaneous abortion, no apparent congenital anomaly * 
1 
Spontaneous abortion with congenital anomaly 
1 
Stillbirth, no apparent congenital anomaly * 
0 
Stillbirth with congenital anomaly 
0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing, lost to follow-up or unknown 
47 
Total 
64 
FluLaval Quadrivalent: 
Overall, as of 31 May 2017, GSK had received 8 reports of exposure to FluLaval 
Quadrivalent during pregnancy since launch on 15 August 2013. At the time of the 
reporting, all 8 pregnancies were ongoing or lost to follow-up. 
7.1.2.3. 
GSK sIIVs 
Animal studies did not reveal any developmental or reproductive safety issue for 
GSK sIIVs. There are, however, no adequate and well-controlled studies of these 
vaccines in pregnant women. Review of the collective post marketing exposure 
experience of GSK sIIVs does not suggest a safety signal. It is not known whether 
GSK sIIVs can have negative effects on human reproductive capacity or pregnancy 

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outcomes. It is generally accepted that inactivated vaccines pose no risk to the pregnant 
or lactating women (Centers for Disease Control and Prevention [CDC, 2002]). 
7.1.3. 
Medical conditions for use (Amended on 27 October 2017) 
The GSK sIIVs are approved by the US Food and Drug Administration (FDA) for 
prevention of disease caused by influenza A subtype viruses and type B 
viruses contained in the vaccines (Table 5). In the US, the GSK sIIVs are 
approved for use in persons 3 years of age and older or 6 months of age 
and older, depending on the vaccine. 
Table 5 
Year of initial US approval for GSK sIIVs 
GSK sIIV 
Initial US Approval 
Fluarix 
2005 
FluLaval 
2006 
Fluarix Quadrivalent 
2012 
FluLaval Quadrivalent 
2013 
7.1.4. 
Characteristics of exposure 
Pregnant women may inadvertently be vaccinated with GSK sIIVs during the first 
trimester, before pregnancy is known. In general, the women are closely monitored 
throughout the remainder of the pregnancy. 
Refer to Section 9.2.1.2 for potential annual exposure in pregnant women. 
7.1.5. 
Potential benefits of product 
Because of the increased rate of hospitalization for serious complications of influenza 
among pregnant women, particularly in the third trimester [Neuzil, 1998], the CDC 
Advisory Committee on Immunization Practices (ACIP) recommends that any woman 
who will be pregnant during the influenza season should be vaccinated for influenza 
[CDC, 2011] and the American College of Obstetrics and Gynecology guidelines indicate 
that pregnant women may be vaccinated with IIV during any trimester [ACOG, 2004]. 
7.2. 
Rationale 
The purpose of this pregnancy registry study is to detect and describe abnormal pregnancy 
outcomes in women intentionally or unintentionally vaccinated with any of the four GSK 
sIIVs. The combination of the large number of women who are of reproductive capacity 
in the indicated age range for vaccination with GSK sIIVs, and the lack of data 
concerning vaccination during pregnancy, makes such a Registry an important 

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component of the ongoing program to assess the safety of these vaccines. This study 
is a transition of existing ongoing pregnancy registries for Fluarix, FluLaval, and 
Fluarix Quadrivalent and an ongoing PASS for FluLaval Quadrivalent into a 
combined PASS for GSK sIIVs.  
The Registry requires voluntary, prospective reporting of eligible pregnancies by 
patients and healthcare professionals (HCPs). Patient confidentiality is strictly 
maintained. The intent of the Registry is to prospectively collect data such as 
vaccination with any of the four GSK sIIVs during pregnancy or within 28 days 
preceding conception, potential confounding factors (such as exposure to other 
medications) and information related to the outcome of the pregnancy. 
The GSK sIIV pregnancy registry study will be maintained by GSK’s Vaccine Clinical 
Safety and Pharmacovigilance (VCSP) department. 
8. 
RESEARCH QUESTION AND OBJECTIVES 
8.1. 
Co-primary objectives 
• 
To describe the characteristics of prospectively reported pregnancies (women 
vaccinated with Fluarix or FluLaval or Fluarix Quadrivalent or FluLaval 
Quadrivalent during pregnancy or within 28 days preceding conception) with 
abnormal pregnancy outcomes. 
• 
To assess the proportion of prospectively reported pregnancies (women vaccinated 
with Fluarix or FluLaval or Fluarix Quadrivalent or FluLaval Quadrivalent during 
pregnancy or within 28 days preceding conception) with abnormal pregnancy 
outcomes. 
Refer to Section 9.3.1 for the definition of the primary endpoint. 
9. 
RESEARCH METHODS 
9.1. 
Study design 
9.1.1. 
Overview (Amended on 27 October 2017) 
• 
This study is a transition of existing ongoing pregnancy registries for Fluarix, 
FluLaval, and Fluarix Quadrivalent and an ongoing PASS for FluLaval 
Quadrivalent into a combined PASS for GSK sIIVs. 
• 
This is an exploratory, prospective, observational, cohort study.  
• 
The GSK sIIV pregnancy registry study requires voluntary, prospective* 
reporting of eligible pregnancies by patients and HCPs. Data such as vaccination 
with a GSK sIIV during pregnancy or within 28 days preceding conception, potential 
confounding factors (such as exposure to other medications) and information related 
to the outcome of the pregnancy will be collected prospectively. 

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*Some pregnancy exposures may be reported when the outcome is unknown 
(prospective reports). 
Some pregnancy exposures may be reported after pregnancy outcome has been 
identified (retrospective reports). The Registry will capture retrospective reports, but 
these reports will not be included in the analyses of prospective reports. 
• 
This study is a post-marketing commitment in the US. 
• 
Study population: pregnant women, vaccinated with GSK sIIV during pregnancy 
or within 28 days preceding conception, volunteering to take part in the study. 
• 
Type of study: self-contained. 
• 
Data collection: initial and follow-up data will be collected using 3 
questionnaires. Data for enrollment will be collected using the Initial 
Notification Form. Follow-up of cases is performed within 2 months of the 
estimated date of delivery (EDD) to ascertain pregnancy outcome (through the 
Pregnancy Outcome Form) and approximately 6 months and 12 months after the 
EDD (for all live births for whom the contact details of their HCP will be available) 
to ascertain the presence of birth defects not diagnosed before (through the 6- and 
12-month post-delivery Follow-Up Form). 
• 
After transition of the ongoing pregnancy registrations into one combined PASS for 
GSK sIIVs, data will be collected for a minimum of 5 years starting Q2 2014. 
9.1.2. 
Rationale for study design 
This is a condition based Registry as opposed to a disease registry. After market 
authorization, adverse events (AEs) that occur after administration of the vaccine can and 
should always be reported. In that case, however, there is no clear group in which the 
events occur and so a proper rate of occurrence cannot be estimated. In this pregnancy 
registry, participants are recruited between administration of the vaccine and the potential 
occurrence of an AE (i.e., a teratogenic effect in the offspring). This allows for a more 
proper estimation of the rate of occurrence of these events. Nevertheless, the results of 
this study still need to be regarded with caution as the exact number of women exposed 
during pregnancy is unknown. Incidences of events cannot therefore be calculated from 
the study data. 
Furthermore, it is likely that pregnant women who accept vaccination may differ from 
those who refuse vaccination in underlying health status, propensity to seek medical care, 
propensity to report AEs and differences in access to medical care in general. The 
differential response/participation by vaccinated versus unvaccinated pregnant women in 
a pregnancy registry could significantly bias risk estimates and possibly in unpredictable 
ways, because of the inability to collect adequate data to characterize the non-responders. 
Therefore, the risks of any identified birth defects will be compared to those in the 
general population, such as that defined by the Metropolitan Atlanta Congenital Defects 
Program (MACDP). 

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9.2. 
Setting 
9.2.1. 
Study population 
9.2.1.1. 
Patient population (Amended on 27 October 2017) 
In the US, the GSK sIIVs are indicated for prevention of disease caused by influenza A 
subtype viruses and type B viruses contained in the vaccine. GSK sIIVs are approved for 
use in persons 3 years of age and older or 6 months of age and older, depending on the 
vaccine. 
The study population includes women vaccinated with any of the four GSK sIIVs 
during pregnancy or within 28 days preceding conception. 
9.2.1.2. 
Potential annual exposure (Amended on 27 October 2017) 
Size of the potential “at-risk” population 
In the year 2012, the fertility rate in the US was 63.2 births per 1000 women aged 
15-44 years and there were 3.96 million births [CDC, 2012]. 
Number of pregnant vaccinees 
The four GSK sIIVs are classified as Pregnancy Category B. Although the number of 
pregnant women who will be vaccinated with GSK sIIV with this registry is impossible to 
predict, experiences with other vaccine pregnancy registries (e.g., smallpox vaccine 
[CDC, 2003], varicella vaccine [Shields, 2001] and Twinrix) indicate that it is likely that 
fewer than 100 pregnancies per year will be registered for each of the vaccines. 
9.2.2. 
Patient recruitment (Amended on 27 October 2017) 
Reporting of vaccine-exposed pregnancies to the Registry is voluntary. Reporters 
become aware of the Registry through the US Prescribing Information (PI) and, in the 
case of healthcare providers, the GSK Registry website. The PIs for each of the sIIVs and 
GSK Registry website each give a brief summary of the purpose and intent of the Registry, 
along with contact information. The forms for enrolling and reporting outcomes are 
also accessible to healthcare providers through the GSK Registry website. 
Additionally, GSK has requested that information regarding GSK pregnancy registries be 
posted directly on the FDA website. 
9.2.3. 
Selection of a comparison group 
This registry study is a prospective cohort study. Active enrollment of a valid internal 
comparison group is not possible. The outcomes of the study will be assessed against 
known rates from an external reference group for the likelihood of a safety signal 
warranting further investigation. Background risks from existing, external systems (e.g., 
the National Birth Defects Prevention Network and the National Center for Health 
Statistics) will be used. 

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9.2.4. 
Study period 
GSK proposes to continue the Registry for a minimum of 5 years (5 influenza seasons), 
starting in Q2 2014. Enrollment is planned to take place during the following Northern 
Hemisphere influenza seasons: 2014-15, 2015-16, 2016-17, 2017-18 and 2018-19. After 
submission of the final report, GSK will continue the Registry pending CBER review of 
the report and determination whether the Registry can be discontinued. 
9.2.5. 
Inclusion criteria (Amended on 27 October 2017) 
A subject will be included in the Registry if all of the following criteria are met: 
• 
Exposure to GSK sIIVs occurs during pregnancy or within 28 days preceding 
conception. 
• 
Subject is a US resident. 
• 
A HCP is identified (name, address and phone number). 
• 
Subject can be identified (by GSK or HCP). 
Data from registered subjects will be included in the analyses if the following criterion is 
met: 
• 
Pregnancy is ongoing and the outcome is unknown at the time of initial report. 
9.2.6. 
Exclusion criterion 
Data from registered subjects will not be included in the analyses if the following 
criterion is met: 
• 
Outcome of pregnancy is known at the time of initial report. Types of known 
outcomes include prenatal testing reports in which the results are abnormal or 
outside the reference range, indicating possible abnormality in the fetus.  
9.3. 
Variables 
9.3.1. 
Primary endpoint 
• 
Occurrence of abnormal pregnancy outcomes in women intentionally or 
unintentionally vaccinated with Fluarix or FluLaval or Fluarix Quadrivalent or 
FluLaval Quadrivalent during pregnancy or within 28 days preceding conception. 
9.3.2. 
Data to be collected (Amended on 27 October 2017) 
Data will be collected using 3 questionnaires; one for enrollment (i.e. Initial Notification 
Form), one for follow-up data after the EDD (i.e. Pregnancy Outcome Form) and one 
for infant data at about 6 and 12 months after EDD (i.e. 6- and 12-month post-delivery 
Follow-Up Form). 

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9.3.2.1. 
Questionnaire for initial data collection (Amended on 27 October 
2017) 
The following data will be collected using the questionnaire for initial data collection (i.e. 
Initial Notification Form): 
• 
Patient identifier. 
• 
Maternal medical and family history including date of birth, date of last 
menstrual period (LMP), EDD, ethnicity. 
• 
Type of conception. 
• 
Prenatal testing. 
• 
Number and outcome of previous pregnancies, including details of birth defects if 
applicable. 
• 
Maternal/paternal history which may have an impact on the outcome of this 
pregnancy. 
• 
Fluarix, FluLaval, Fluarix Quadrivalent or FluLaval Quadrivalent vaccination 
including lot number and date of administration. 
• 
Other drug/vaccine exposure including drug/vaccine name, route of administration, 
dose, lot number, indication and date of administration. 
• 
Occurrence of AEs (if any), including onset/end date, outcome and relationship to 
GSK products. 
• 
Name of HCP supervising pregnancy and contact information, if available. 
• 
Any additional data that seems relevant for this study. 
9.3.2.2. 
Questionnaire for pregnancy outcome data collection (Amended on 27 
October 2017) 
The following follow-up data will be collected using the questionnaire for pregnancy 
outcome data collection (i.e. Pregnancy Outcome Form): 
• 
Pregnancy outcome. 
• 
Method of delivery. 
• 
Fetal/neonatal status, including description of birth defects if applicable. 
• 
Infant information including gestational weeks at birth/miscarriage/termination, 
gender, length, weight, Apgar score. 
• 
Additional drug/vaccine exposure including drug/vaccine name, route of 
administration, dose, lot number, indication and date of administration. 
• 
AEs experienced by the fetus/infant or the mother. 
• 
Name of the HCP supervising the infant and contact information, if available. 
• 
Any additional data that seems relevant for this study. 

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9.3.2.3. 
Questionnaire for infant data collection 
The following data on the infant will be collected using the questionnaire for 6- and 
12-month after delivery follow-up data collection (i.e. 6 and 12-month post-delivery 
Follow-Up Form): 
• 
Infant status, including description of birth defects not diagnosed at the time of 
the initial follow-up, if applicable. 
• 
AEs experienced by the infant. 
• 
Additional drug/vaccine exposure including drug/vaccine name, route of 
administration, dose, lot number, indication and date of administration. 
• 
Any additional data that seems relevant for this study. 
9.4. 
Data sources (Amended on 27 October 2017) 
Reporting of vaccine-exposed pregnancies to the Registry is voluntary. Registration 
can be initiated from a HCP, their staff or from a consumer. Permission from 
consumers is requested to obtain confirmation and follow-up from their HCP, as 
well as follow-up from the HCP participating in the care of the infant. A toll-free 
telephone number for reporting AEs and vaccine-exposed pregnancies to the Registry 
are listed in the product information leaflets and on the GSK Registry website. 
Retrospective post-marketing reports and relevant scientific publications are potential 
sources of additional information. 
9.5. 
Study size 
No minimum sample size is required for this registry study. 
Refer to Section 9.2.1.2 for the size of the potential “at-risk” population and the 
number of pregnant vaccinees. 
9.6. 
Data management 
9.6.1. 
Data collection (Amended on 27 October 2017) 
Initial and follow-up data will be collected using 3 questionnaires. Initial data will be 
collected before the outcome is known. Follow-up of cases is performed at the 
following timepoints: 
For consumer reports: 
• 
At initial notification of pregnancy exposure: 2 attempts at 4-6 week intervals 
will be made to obtain more information about the pregnancy (e.g. estimated 
time of delivery (EDD) and/or last menstrual period (LMP) and to obtain 
permission to contact the patient’s HCP 

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• 
Within 2 months after EDD: 1 additional attempt is made, if permission to 
contact the patient’s HCP has not already been granted, to obtain more 
information about the pregnancy and obtain the permission to contact the 
patient’s HCP. 
• 
Within 2 months after EDD (and if the patient has not previously provided the 
contact information for her infant’s HCP): 2 attempts at 4-6 week intervals 
will be made for all live births to obtain the contact information of the HCP 
supervising the health of the infant. 
For HCP reports: 
• 
At initial notification of pregnancy exposure or once permission has been 
granted for reports initially received from a consumer, 2 attempts at 4-6 week 
intervals will be made to obtain more information via pregnancy follow-up 
form.  
For all reports: 
• 
Within 2 months of the EDD, to ascertain outcome. Two attempts to obtain 
outcome information will be made before any case is considered lost to follow-up. 
• 
An additional follow-up will be done for all live births (as confirmed around EDD) 
at approximately 6 months after the EDD to ascertain the presence of birth defects 
not diagnosed at the time of the initial follow-up. For this follow-up, the HCP 
supervising the health of the infant will be contacted. 
• 
The last follow-up will be done for all live births (as confirmed around EDD) at 
approximately 12 months after the EDD to ascertain the presence of birth defects not 
diagnosed at previous follow-ups. This follow-up will be done regardless of whether 
or not follow-up information was received at approximately 6 months after the 
EDD. For this follow-up, the HCP supervising the health of the infant will be 
contacted. 
9.6.2. 
Processing of reports (Amended on 27 October 2017) 
Reports are entered into the GSK safety database by the GSK Case Management 
Group responsible for all case entry into GSK’s worldwide safety database using 
existing mechanisms and practices. Follow-up is conducted by the Case Management 
Group.  
The HCP supervising the pregnancy is contacted if she/he requests or if initial 
information is insufficient or needs clarification. The HCP supervising the health of 
the infant (and/or their staff) is contacted for all live births and if permission has 
been granted by the mother. 

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9.6.2.1. 
Solicitation of outcomes (Amended on 27 October 2017) 
As explained in section 9.6.1, within two months after the EDD and if the HCP has not 
already provided the outcome, she/he is sent a pregnancy outcome form 
(questionnaire). The mode of communication is generally via a standard letter. 
Two attempts are made to secure the outcome information from the HCP. The second 
attempt also utilizes standard letter as mode of contact. For all live births (as confirmed 
around EDD) if the pregnant subject has previously provided her consent but has 
not already shared the contact information for the HCP supervising the health of 
the infant, two attempts are made to obtain this information. 
For all live births (as confirmed around EDD) and with the mother’s permission, two 
attempts are made to solicit information from the pediatrician and/or other specialists who 
have provided healthcare/consultation to the child up until 12 months of age (one 
attempt at around 6 months after EDD and another attempt at around 12 months 
after EDD). 
9.6.2.2. 
Classification of outcomes  
This Registry uses the term ‘birth defects’ for outcomes sometimes referred to as 
‘congenital anomalies’. For purposes of analysis, pregnancy outcomes are 
dichotomized according to the presence or absence of birth defects. The latter group is 
further categorized as: 1) live births, 2) spontaneous abortions (i.e., pregnancy losses) 
and 3) induced abortions. 
This Registry adopts a definition of a child with a birth defect as any live or stillborn 
neonate with a structural or chromosomal abnormality diagnosed before 6 years of age. 
The Registry employs a conservative approach of including all morphologic 
anomalies, including minor ones, as birth defects. To provide consistency in the 
definitions of major defects in this Registry, CDC MACDP criteria are used for the 
classification of defects [CDC, 2008; Correa-Villasenor, 2003]. Some of the conditions 
excluded from the MACDP criteria for major structural defects may actually have major 
clinical, functional, or genetic significance. Therefore, minor malformations not 
appearing in the CDC Inclusion List may be classified as birth defects in this Registry. In 
addition, CDC guidelines disqualify as defects those findings that are present in infants 
delivered at less than 36 weeks of gestation and are attributable to prematurity itself, such 
as a patent ductus arteriosus or inguinal hernias. Infants with infectious conditions (e.g., 
neonatal sepsis) or isolated biochemical abnormalities (e.g., hyperbilirubinemia) are 
classified as being without birth defects unless there is a possibility that the condition 
reflects an unrecognized congenital abnormality. All other congenital abnormalities are 
included in the ‘birth defects’ category, regardless of whether the neonate is delivered 
alive, including structural defects in neonates delivered prior to 20 weeks of gestation or 
weighing less than 500 g. 

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9.7. 
Data analysis (Amended on 27 October 2017) 
Pregnancy outcomes include spontaneous abortion (pregnancy loss before 22 weeks 
gestation), fetal deaths/stillbirths (loss at or after 22 weeks gestation), 
elective/therapeutic abortions and live births. Gestational weeks are counted from the 
date of the LMP. The second trimester is considered to begin at week 14 and the third 
trimester begins at week 28. The presence or absence of birth defects or other 
abnormalities is evaluated within each of the preceding outcome categories. 
Pregnancy outcomes are stratified by the trimester of exposure, with an additional 
stratum for preconception exposure with no subsequent administration of vaccine during 
pregnancy. Receiving multiple administrations of GSK sIIV during a single pregnancy 
is unlikely; however, if this does occur, reports of multiple exposures during a 
pregnancy are classified by the earliest trimester of exposure.  
The calculations of risk for birth defects are made by dividing the number of infants with 
birth defects by the total number of infants with and without birth defects. Since the 
presence of birth defects will be assessed around EDD and at approximately 6 and 12 
months after the EDD (for all live births), the calculation of risk will be performed for 
two separate cohorts: 1). the risk of birth defects for all subjects who completed the 
outcome form at around EDD (regardless of whether they were lost-to-follow up 
afterwards) and 2). the risk of birth defects for all subjects reporting live births and 
who completed either or both the 6- and 12-month post-delivery follow-up forms. 
The outcomes of the study will be assessed against known rates from an external 
reference group for the likelihood of a safety signal warranting further investigation. In 
each periodic and the final reports, the data will be analyzed for all GSK sIIVs pooled 
and for each of the 4 vaccines separately. The analyses will also include data collected 
cumulatively in each individual registry up to the initiation of the combined Registry for 
GSK sIIVs. Individual reports of birth defects following vaccination with any of the 
GSK sIIVs will also be evaluated for causal assessments, as appropriate. 
The majority of spontaneous abortions occur early in pregnancy [Wilcox, 1981; 
Wilcox, 1983; Ellish, 1996]. If spontaneous abortions were to be evaluated as an 
outcome of interest, it would be essential to enroll pregnancies as soon as possible after 
vaccination with GSK sIIV. Because enrollment and recognition of pregnancy would 
occur at various times, it would be virtually impossible to meaningfully evaluate the 
effects of GSK sIIV on pregnancy loss [Kennedy, 2004]. Therefore, spontaneous 
abortions without birth defects are excluded from the risk calculations. 
The risk in the general population of all birth defects meeting CDC criteria is 
approximately 3% (1 of 33) of live births [CDC, 2013]. The estimated risk cited in the 
medical literature varies because of differences in case definitions, populations sampled 
and ascertainment methods. The Collaborative Prenatal Project, using a broader case 
definition and prospective ascertainment, reports a frequency of 5% to 7% [Chung, 
1975]. Most major structural defects originate during the first trimester of pregnancy, 
which is the critical time for organogenesis [Niebyl, 2012]. For such defects, exposures 
occurring in the second or third trimester are not likely to be causally associated. 

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However, for the sake of completeness and to enable the assessment of possible increases 
in the frequency of birth defects, all defects will be included in the periodic summary 
reports of this Registry and stratified by trimester of exposure. 
Criteria for review of a specific individual report include: 
• 
Is the timing of the vaccination with GSK sIIVs commensurate with the 
ontogenetic development of the organ(s) affected by the abnormalities? 
• 
Is there another known or likely cause (e.g., pre-existing genetic or chromosomal 
defect or exposure to a known teratogen)? 
• 
Is the congenital abnormality not previously described (i.e., is it new to medical 
science)? 
• 
Is there a unique constellation of defects (i.e., is there a new syndrome)? 
Criteria for review of aggregate data include: 
• 
Is there a deviation from the expected frequency of all defects indicating an 
increase in the overall risk of defects? 
• 
Is there a deviation from the expected frequencies of individual defects? 
• 
Is there uniqueness (e.g., a pattern) of the abnormalities that is suggestive of a common 
etiology? 
Studies have shown the risk of spontaneous abortion is high early in pregnancy and 
decreases substantially from week 8 to week 28, yielding a cumulative estimated risk of 
10% to 22% [Wilcox, 1981; Wilcox, 1983; Wilcox, 1988; Fenster, 1997; Windham, 
1997; Khattak, 1999; Anderson, 2000; Osborn, 2000]. 
While the Registry is to be limited to prospective reports, some pregnancy exposures are 
reported after pregnancy outcome has been identified (retrospective reports). The 
Registry will capture retrospective reports, but these reports will not be included in the 
analyses of prospective reports. In general, retrospective notification of outcomes 
following exposure to drugs or vaccines is biased toward reporting the severe and 
unusual cases and is not reflective of the general experience with the drug. Information 
about the total number of exposed pregnancies, i.e., the pool of exposures from which the 
retrospective reports arise, is unknown; therefore, incidences of outcomes cannot be 
calculated from these data. A series of reported birth defects, however, can be analyzed to 
detect patterns of specific congenital abnormalities and can identify early signals of new 
vaccine-associated risks. A section of each periodic summary report, separate from the 
analysis of prospective reports, will describe all abnormal outcomes of retrospectively 
reported cases. 
9.8. 
Quality control 
Data will be recorded using questionnaires. Subject data necessary for analysis, follow-up 
and reporting will be entered/transmitted into a validated database or data system. Data 
management will be performed in accordance with applicable GSK standards. 

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To ensure compliance with Good Clinical Practice (GCP) and all other applicable 
guidelines and regulatory requirements, GSK may conduct a quality assurance audit. 
Regulatory agencies may also conduct a regulatory inspection of this study. Such 
audits/inspections can occur at any time during or after completion of the study. 
9.9. 
Limitations of the research methods 
This Registry is a prospective voluntary study. Active enrollment of a valid internal 
comparison group is not possible. Therefore, background risks from existing, external 
systems (e.g., the National Birth Defects Prevention Network and the National Center for 
Health Statistics) are used. The potential limitations of comparisons between Registry 
and background data depends upon the event(s) being compared and will be discussed on 
an ad hoc basis in the relevant periodic Registry reports. In addition, variations in the 
year-to-year (or strain), resulting in differences in the safety profiles of the vaccines, 
remain a possible limitation. 
Refer to Section 9.1.2 for other potential limitations of the study. 
10. 
PROTECTION OF HUMAN SUBJECTS 
10.1. 
Regulatory and ethical considerations, including the 
informed consent process 
The study will be conducted in accordance with the International Conference on 
Harmonization (ICH) Guideline for GCP or other applicable guidelines, all applicable 
subject privacy requirements and the guiding principles of the Declaration of Helsinki. 
The study has been designed and will be conducted in accordance with the ICH 
Harmonized Tripartite Guideline for clinical investigation of medicinal products in the 
pediatric population (ICH E11) and all other applicable ethical guidelines. 
GSK will obtain favorable opinion/approval to conduct the study prior to study start or 
will document that neither a favorable opinion nor an approval to conduct the study is 
needed. 
Conduct of the study includes, but is not limited to, the following: 
• 
Institutional Review Board review and favorable opinion/approval of study protocol 
and any subsequent amendments; 
• 
Institutional Review Board review and favorable opinion/approval of waiver for 
documentation of informed consent. 

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11. 
MANAGEMENT AND REPORTING OF ADVERSE 
EVENTS/ADVERSE REACTIONS 
Reporting of vaccine-exposed pregnancies to the Registry is voluntary. All reports 
received by the Registry will be entered into the GSK safety database and reported to 
regulatory authorities according to applicable regulations. 
12. 
PLANS FOR DISSEMINATING AND COMMUNICATING 
STUDY RESULTS (AMENDED ON 27 OCTOBER 2017) 
Study information from this protocol will be posted on publicly available clinical trial 
registers following finalization of the protocol and, whenever possible, before initiation 
of the study. 
GSK plans to continue the Registry for a minimum of 5 years. Summary reports will be 
written annually and will be submitted with the Periodic Benefit-Risk Evaluation Report 
for each GSK sIIV. Each report will summarize the adverse pregnancy outcomes that 
have been identified since the previous report and will also summarize cumulative results 
since the inception of the individual Registry. A final report will be written and submitted 
to CBER after the 5th annual report. In each periodic and the final reports, the data will be 
analyzed for all GSK sIIVs pooled and for each of the 4 vaccines separately. The 
analyses will also include data collected cumulatively in each individual registry up to the 
initiation of the combined Registry for GSK sIIVs. After submission of the final report, 
GSK will continue the Registry pending CBER review of the report and determination 
whether the Registry can be discontinued. 
Summary results of observational studies that are designed to inform the safety or 
effectiveness, including cost-effectiveness, of GSK vaccines/products as used in ordinary 
clinical practice are publicly registered within 8 months of completion of the analysis. 
GSK also aims to publish the results of these studies in the searchable, peer reviewed 
scientific literature; manuscripts are submitted within 18 months of the completion of the 
analysis. 
13. 
REFERENCES 
American College of Obstetricians and Gynecologists (ACOG) Influenza vaccination 
during pregnancy. ACOG Committee Opinion No. 305. Obstet Gynecol 2004; 104: 
1125-1126. 
Anderson AN, Wohlfahrt J, Christens P, Olsen J, Melbye M. Maternal age and fetal 
loss: population based register linkage study. BMJ 2000; 320:1708-1712. 
Centers for Disease Control and Prevention (CDC). General Recommendations on 
Immunization. Recommendations of the Advisory Committee on Immunization Practices 
and the American Academy of Family Physicians. MMWR 2002; 51 (RR2): 1-36. 

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Centers for Disease Control and Prevention (CDC). Women with smallpox vaccine 
exposure during pregnancy reported to the National Smallpox Vaccine Pregnancy Registry 
-- United States, 2003. MMWR 2003; 52: 386-388. 
Centers for Disease Control and Prevention (CDC). Birth Defects and Genetic Diseases 
Branch 6-digit code for reportable congenital anomalies. Revised 2008.  
Available at http://www.cdc.gov/ncbddd/birthdefects/documents/MACDPcode0807.pdf 
Accessed 22 August 2013. 
Centers for Disease Control and Prevention (CDC). Influenza Vaccination Coverage 
Among Pregnant Women-United States, 2010–11 Influenza Season. MMWR 2011; 60: 
1078-1082. 
Centers for Disease Control and Prevention (CDC). Recent Trends in Births and Fertility 
Rates Through December 2012. Available at 
http://www.cdc.gov/nchs/data/hestat/births_fertility_december_2012/births_fertility_decem
ber_2012.htm 
Accessed 29 August 2013. 
Centers for Disease Control and Prevention (CDC). Birth defects. 
Available at http://www.cdc.gov/ncbddd/birthdefects/index.html 
Accessed 22 August 2013. 
Chung CS, Myrianthopoulos NC. Factors affecting risks of congenital malformations: 
Reports from the Collaborative Perinatal Project. Birth Defects Original Article Series 1975; 
11(10): 1-22. 
Correa-Villasenor A, Cragan J, Kucik J, O'Leary L, Siffel C, Williams L. The 
Metropolitan Atlanta Congenital Defects Program: 35 years of birth defects surveillance 
at the Centers for Disease Control and Prevention. Birth Defects Research (Part A) 
2003; 67: 617-624. 
Ellish NJ, Saboda K, O'Connor J, et al. A prospective study of early pregnancy loss. 
Hum Reprod 1996; 11: 406-412. 
Fenster L, Hubbard AE, Windham GC, Waller KO, Swan SH. A prospective study of 
work-related physical exertion and abortion. Epidemiology 1997; 8: 66-74. 
Fluarix PI, 2013. Available at http://us.gsk.com/products/assets/us_fluarix.pdf 
Accessed 13 February 2014. 
Fluarix Quadrivalent PI, 2013. . Available at 
http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/U
CM220624.pdf 
FluLaval PI, 2013. Available at http://us.gsk.com/products/assets/us_flulaval.pdf 
Accessed 13 February 2014. 

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FluLaval Quadrivalent PI, 2013. Available at 
http://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/U
CM366070.pdf 
Accessed 13 February 2014. 
Honein MA, Paulozzi LJ, Cragan JD, Correa A. Evaluation of selected characteristics of 
pregnancy drug registries. Teratology 1999; 60(6): 356-364. 
Kennedy DL, Uhl K, Kweder SJ. Pregnancy exposure registries. Drug Safety 2004; 27: 
215-228. 
Khattak S, K-Moghtader G, McMartin K, Barrera M, Kennedy D, Koren G. Pregnancy 
outcome following gestational exposure to organic solvents. JAMA 1999; 281(12): 1106-
1109. 
Neuzil KM, GW Reed, EF Mitchel, L Simonsen, MR Griffin. Impact of influenza on 
acute cardiopulmonary hospitalizations in pregnant women. Am J Epidemiol 1998; 148: 
1094-1102. 
Niebyl JR and JL Simpson. Chapter 8: Drugs and environmental agents in pregnancy and 
lactation: embryology, teratology and epidemiology. In Gabbe: Obstetrics: Normal and 
problem pregnancies, 6th ed; 2012: Saunders (Elsevier) p. 141.  
Osborn JF, Cattaruzza MS, Spinelli A. Risk of spontaneous abortion in Italy, 1978-1995, 
and the effect of maternal age, gravity, marital status and education. Am J Epidemiol 
2000; 151: 98-105. 
Shields KE, Galil K, Seward J, et al. Varicella vaccine exposure during pregnancy: Data 
from the first 5 years of the Pregnancy Registry. Obstet Gynecol 2001; 98: 14-19. 
Wilcox AJ, Treloar AE, Sandler DP. Spontaneous abortion over time: comparing 
occurrence in two cohorts of women a generation apart. Am J Epidemiol 1981; 
114(4): 548-553. 
Wilcox AJ. Surveillance of pregnancy loss in human populations. Amer J Industr Med 
1983; 4: 285-291. 
Wilcox AJ, Weinberg CR, O'Connor JF, et al. Incidence of early loss of pregnancy. New 
Engl J Med 1988; 319: 189-194. 
Windham GC, Von Behren J, Fenster L, Schaefer C, Swan SH. Moderate maternal 
alcohol consumption and risk of spontaneous abortion. Epidemiology 1997; 8: 509-514. 

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ANNEX 1 List of stand-alone documents 
No. 
Document Reference No 
Date 
Title 
1 
201476 (EPI-FLU-039 VS US PR) 
13-MAY-2014 
List of stand-alone documents 
2 
201476 (EPI-FLU-039 VS US PR) 
13-MAY-2014 
ENCePP Checklist for study protocols 
3 
201476 (EPI-FLU-039 VS US PR) 
13-MAY-2014 
Glossary of terms 
4 
201476 (EPI-FLU-039 VS US PR) 
11-OCT-2017 
Amendments and administrative changes to 
the protocol 
5 
201476 (EPI-FLU-039 VS US PR) 
13-MAY-2014 
Trademarks 
6 
201476 (EPI-FLU-039 VS US PR) 
13-MAY-2014 
Protocol Sponsor Signatory Approval 

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ANNEX 2 ENCePP Checklist for study protocols 

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ANNEX 3 Glossary of terms 
Adverse event: 
Any untoward medical occurrence in a subject, 
temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal 
product, or temporally associated with a study procedure. 
An AE can therefore be any unfavorable and unintended 
sign (including an abnormal laboratory finding), 
symptom, or disease (new or exacerbated) temporally 
associated with the use of a medicinal product. For 
marketed medicinal products, this also includes failure to 
produce expected benefits (i.e., lack of efficacy), abuse or 
misuse. 
eTrack: 
GSK Biologicals’ tracking tool for clinical/ 
epidemiological trials. 
GSK seasonal 
Inactivated Influenza 
Vaccines (GSK sIIVs): 
Fluarix®/ FluLaval®/ Fluarix® Quadrivalent/ FluLaval® 
Quadrivalent vaccines 
Non-interventional 
(observational) Human 
Subject Research: 
Studies where medicinal products, should they be 
administered, are prescribed in normal (routine) medical 
practice. No medical care or medical/scientific procedures 
as required in a research protocol are administered to 
participants except as part of routine medical care. 
Post-Authorization 
Safety Study (PASS): 
A pharmaco-epidemiological study or a clinical trial 
carried out in accordance with the terms of the marketing 
authorization, conducted with the aim of identifying or 
quantifying a safety hazard relating to an authorized 
medicinal product. This includes all GSK sponsored non-
interventional studies and clinical trials conducted 
anywhere in the world that are in accordance with the 
terms of the European marketing authorization and where 
the investigation of safety is the specific stated objective. 
Note: The phrase ‘In accordance with the terms of the 
European marketing authorization’ means that the 
product is used according to the European label (e.g., 
within the recommended dose range, the approved 
formulation, indication etc.). 
Prospective study: 
A study that looks ahead for outcomes, e.g., the 
development of a disease, during the study period and 
relates this to other factors such as a potential risk due to 
exposure or protection factor(s). The study usually 
involves taking a cohort of subjects and watching them 

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over a period for one or more common outcomes of 
interest. 
Protocol amendment: 
The International Conference on Harmonization (ICH) 
defines a protocol amendment as: ‘A written description 
of a change(s) to or formal clarification of a protocol.’ 
GSK Biologicals further details this to include a change 
to an approved protocol that affects the safety of subjects, 
scope of the investigation, study design, or scientific 
integrity of the study. 
Research protocol: 
A document that describes the objective(s), design, 
methodology, statistical considerations and organization 
of a study. The protocol usually also gives the 
background and rationale for the study, but these could be 
provided in other protocol referenced documents. 
Retrospective study: 
A study that looks backward in time (e.g., at events that 
occurred in the past; outcomes and exposure can no 
longer be influenced), usually using medical records, 
databases or interviews in order to address one or more 
study objectives. 
Self-contained study: 
Study with objectives not linked to the data of another 
study. 
Study population: 
Sample of population of interest. 
Subject: 
Term used throughout the protocol to denote an 
individual who has been contacted in order to participate 
or participates in the epidemiological study or a person 
about whom some medical information has been recorded 
in a database. 

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ANNEX 4 Amendments and administrative changes to the 
protocol 
GlaxoSmithKline Biologicals SA 
Vaccines R & D  
Protocol Amendment 1 
eTrack study number and 
Abbreviated Title: 
201476 (EPI-FLU-039 VS US PR) 
Amendment number: 
Amendment 1 Final 
Amendment date: 
27 October 2017 
Co-ordinating author: 
, Scientific Writer 
Rationale/background for changes:  
PPD

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The current protocol is being amended to correct the following: 
Data collection: 
• 
Corrections were made throughout the protocol to reflect current practices for data 
collection, that two and not three follow up attempts are made around EDD to 
ascertain the presence of birth defects.  
• 
Follow-up questionnaires for all live births were not being sent at approximately 6 
and 12 months after EDD to ascertain the presence of birth defects not diagnosed 
at around EDD, contrary to what was described in the protocol. The importance of 
this information is acknowledged and both 6- and 12-month follow-up attempts 
will be implemented prospectively via a new data collection form. 
• 
Originally, pregnant subjects enrolled into the registry had to sign a consent form 
only when subjects registered themselves into the registry, and to allow GSK to 
contact their HCPs at around EDD. Now, HCPs who register their pregnant 
patients will be encouraged to provide these with the consent form. With this 
consent, the HCP supervising the health of the infant up can also be contacted until 
12 months after delivery. The consent form for the registry has also been refined to 
attempt to obtain contact information on the infant’s healthcare provider. This new 
consent form will be implemented for all prospective reports. 
Exclusion criterion: 
• 
According to the exclusion criterion detailed in section 9.2.6 for the original 
protocol, subjects should be excluded from the registry if prenatal tests exist at the 
time of enrollment suggesting either normal or abnormal results. Considering that 
most pregnancies in the US go through fetal ultrasounds by the first trimester of 
gestation, this exclusion criterion will pointedly limit the number of subjects who 
enroll into the registry and enrich for subjects with low prenatal care coverage. 
The registry protocol has been updated to reflect its current practices: pregnancies 
will be excluded from enrollment only if abnormal pregnancy outcomes are 
diagnosed before receipt of a GSK seasonal influenza vaccine. 
Pregnancy registry reports: 
• 
The dates for submission of the annual reports have been updated to reflect newer 
PBRER submission dates.  

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Post-marketing exposure in pregnant women: 
• 
Numbers and outcomes of women exposed to each GSK sIIV during pregnancy 
since their respective launches and spontaneously reported into our safety database 
worldwide were updated. 
Data Analysis: 
• 
Since the 6- and 12-month follow-ups will only be done prospectively, we propose 
calculating the risk of birth defects for two separate cohorts: 1). the risk of birth 
defects for all mother-child pairs with complete pregnancy outcome forms at 
around EDD (regardless of whether they were lost-to-follow up afterwards) and 2). 
the risk of birth defects for all mother-child pairs reporting live births at around 
EDD and who completed either or both the 6- and 12-month post-delivery follow-
up forms.  
Since this registry is currently ongoing, changes beyond those related to the items 
above were limited to minor updates for clarity purposes. 
These changes will be implemented within 30 days of approval by the FDA. 
Amended text has been included in bold italics and deleted text in strikethrough in 
the following sections: 
Cover page: 
Authors 
• 
, Safety Scientist, 
Safety Evaluation & Risk Management, 
Vaccine Clinical Safety and 
Pharmacovigilance 
• 
, Head, Safety Evaluation & 
Risk Management, Vaccine Clinical Safety 
and Pharmacovigilance 
• 
, Local Medical Lead 
• 
, Clinical and Epidemiology 
Project Lead, Influenza Vaccines 
• 
, Regulatory Affairs 
• 
, Manager, CMG 
• 
, Clinical Safety Associate 
• 
, Director, CMG 
• 
, Study Delivery 
Lead 
• 
, Senior Epidemiology 
Expert, US RDC 
• 
, Lead Epidemiologist 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD

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Copyright 2014 of the GlaxoSmithKline group of companies. All rights reserved. Unauthorized copying 
or use of this information is prohibited 
© [2014-2017] GSK group of companies or its licensor 
Synopsis: 
Study design  
• 
This study is a transition of existing ongoing pregnancy 
registries for Fluarix, FluLaval and Fluarix 
Quadrivalent and an ongoing PASS for FluLaval 
Quadrivalent into a combined PASS for these four GSK 
sIIVs. 
• 
This is an exploratory prospective, observational, cohort 
study. The GSK sIIVs pregnancy registry study requires 
voluntary, prospective* reporting of eligible pregnancies 
by patients and healthcare professionals (HCPs). Data such 
as vaccination with GSK sIIVs during pregnancy or within 
28 days preceding conception, potential confounding factors 
(such as exposure to other medications) and information 
related to the outcome of the pregnancy will be collected 
prospectively. 
*Some pregnancy exposures may be reported when the 
outcome is unknown (prospective reports). 
Some pregnancy exposures may be reported after 
pregnancy outcome has been identified (retrospective 
reports). The Registry will capture retrospective reports, 
but these reports will not be included in the analyses of 
prospective reports. 
• 
This study is a post-marketing commitment in the US. 
• 
Study population: pregnant women, vaccinated with GSK 
sIIVs during pregnancy or within 28 days preceding 
conception volunteering to take part in the study. 
• 
Type of study: self-contained. 
• 
Data collection: initial and follow-up data will be 
collected using questionnaires (Registration Initial 
notification form, Pregnancy Outcome form and 6 and 
12-month post-delivery follow-up form). Initial data 
can be collected from pregnant subjects, their 
healthcare providers or both. Follow-up of cases is 
performed within 2 months of the estimated date of 
delivery (EDD) to ascertain outcome and approximately 
6 months and 12 months after the EDD (for all live births 
for whom the contact details of their HCP will be 
available) to ascertain the presence of birth defects not 
diagnosed before. Follow-up questionnaires can only be 
completed by healthcare providers and/or HCP staff 

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participating in the care of the pregnant female or 
offspring, as applicable. 
• 
After transition of the ongoing pregnancy registries into 
one combined PASS for GSK sIIVs, data will be collected 
for a minimum of 5 years starting Q2 2014 
Population, 
including the 
setting and study 
population 
In the US, GSK sIIVs are indicated for prevention of disease 
caused by influenza A subtype viruses and type B viruses 
contained in the vaccine. GSK sIIVs are approved for use in 
persons 3 years of age and older. Currently, GSK sIIVs are 
approved for use in persons 3 years of age and older or 6 
months of age and older, depending on the vaccine. 
Size of the potential “at-risk” population 
In the year 2012, the fertility rate in the US was 63.2 births 
per 1000 women aged 15-44 years and there were 3.96 
million births [CDC, 2012]. 
Number of pregnant vaccinees 
Although the number of pregnant women who will be 
vaccinated with GSK IIVs through this registry is impossible to 
predict, experiences with other vaccine pregnancy registries 
indicate that it is likely that fewer than 100 pregnancies per 
year will be registered for each of the vaccines. 
Data sources 
Reporting of vaccine-exposed pregnancies to the Registry is 
voluntary. Registration can be initiated from a HCP or from 
a consumer in the latter case. Permission from consumers is 
requested to obtain confirmation and follow-up from their 
HCP, as well as follow-up from the HCP of their infant. A 
toll-free telephone number for reporting adverse events 
(AEs) and vaccine-exposed pregnancies to the Registry are 
listed in the product information leaflet and on the GSK 
Registry website. Retrospective post-marketing reports and 
relevant scientific publications are potential sources of 
additional information. 
Data analysis 
Pregnancy outcomes include spontaneous abortion 
(pregnancy loss before 20 22 weeks gestation), fetal 
deaths/stillbirths (loss at or after 20 22 weeks gestation), 
elective/therapeutic abortions and live births. The presence 
or absence of birth defects or other abnormalities is 
evaluated within each of the preceding outcome categories. 
Pregnancy outcomes are stratified by the trimester of 
exposure, with an additional stratum for preconception 
exposure with no subsequent administration of vaccine 

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during pregnancy. Reports of multiple exposures during a 
pregnancy are classified by the earliest trimester of 
exposure. The calculations of risk for birth defects are made 
by dividing the number of infants with birth defects by the 
total number of infants with and without birth defects. An 
exact 95% confidence interval is calculated using standard 
statistical software. The outcomes of the study will be 
assessed against known rates from an external reference 
group for the likelihood of a safety signal warranting further 
investigation. 
Spontaneous abortions without birth defects are excluded 
from the risk calculations. 
All defects regardless of trimester of vaccine exposure will 
be included in the periodic summary reports of this Registry 
and stratified by trimester of exposure. 
A section of each periodic summary report, separate from 
the analysis of prospective reports, will describe all 
abnormal outcomes of retrospectively reported cases. 
Milestones 
Summary reports with cumulative analyses will be written 
annually and submitted with the Periodic Benefit-Risk 
Evaluation Report (PBRER) for each GSK sIIV. A final 
report will be written and submitted 18 months after the last 
annual report. A final report will be written and submitted 
18 months after the last annual report. 
After submission of the final report, GSK will continue the 
Registry pending Center for Biologics Evaluation and 
Research (CBER) review of the report and determination 
whether the Registry can be discontinued. 
Section 6 
Milestones 

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Milestone 
Planned date a 
Start of data collection 
01 June 2014 b 
End of data collection 
31 May 2019 c 
Annual report 1 (2014-2015 influenza season) 
10 February 2016 30 June 2015 
Annual report 2 (2015-2016 influenza season) 
10 February 2017 30 June 2016 
Annual report 3 (2016-2017 influenza season) 
10 February 2018 30 June 2017 
Annual report 4 (2017-2018 influenza season) 
10 February 2019 30 June 2018 
Annual report 5 (2018-2019 influenza season) 
30 June 2019 10 February 2020 
Final report  
August 2021  06 March 2020 
a The Fluarix and FluLaval Registries were originally initiated on 02 Sep 2011. The Fluarix Quadrivalent and 
FluLaval Quadrivalent Registries were originally initiated on 30 Aug 2013 and 30 Nov 2013, respectively. In 
2014. the ongoing Registries will be were combined and converted into a PASS. GSK plans to continue the 
Registry for a minimum of 5 years, starting Q2 2014. 
b Women vaccinated with GSK sIIVs during pregnancy or within 28 days preceding conception, reported before 
the planned date of start of data collection (01 June 2014) but for which the pregnancy outcome is not yet 
known, may be enrolled retroactively in the Registry. 
c After submission of the final report, GSK will continue the Registry pending Center for Biologics Evaluation and 
Research (CBER) review of the report and determination whether the Registry can be discontinued. 
Section 7.1.1.2 
Post marketing exposure in pregnant women 

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Fluarix: 
Overall, as of 31 August 2013 31 May 2017, GSK had received 243 236 reports of 
exposure to Fluarix during pregnancy since its launch on 04 July 1991. The outcomes of 
the 243 236 pregnancies are summarized in Table 2. 
Table2  
Outcomes of pregnancy exposed to Fluarix 
Outcome 
Number of Cases  
since launch (n) 
Live infant, no apparent congenital anomaly * 
55 52 
Live infant with congenital anomaly 
4 1 
Elective termination, no apparent congenital anomaly * 
1 0 
Elective termination with congenital anomaly 
2 1 
Spontaneous abortion, no apparent congenital anomaly * 
12 8 
Spontaneous abortion with congenital anomaly 
0 1 
Stillbirth, no apparent congenital anomaly * 
2 0 
Stillbirth with congenital anomaly 
1 0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing, lost to follow-up or unknown 
166 173 
Total 
243 236 
* Pregnancy outcome categories stating no apparent congenital anomaly include outcomes where it is unknown 
whether a congenital anomaly occurred. 
FluLaval: 
Overall, as of 17 December 2013 31 May 2017, GSK had received 128 130 reports of 
exposure to FluLaval during pregnancy since launch on 18 December 1992. The 
outcomes of the 128 130 pregnancies are summarized in Table 3. 

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Table 3 
Outcomes of pregnancy exposed to FluLaval 
Outcome 
Number of Cases  
since launch 
Live Infant, no apparent congenital anomaly * 
26 46 
Live infant with congenital anomaly 
2 1 
Elective termination, no apparent congenital anomaly * 
0 
Elective termination with congenital anomaly 
0 
Spontaneous abortion, no apparent congenital anomaly * 
3 
Spontaneous abortion with congenital anomaly 
0 
Stillbirth, no apparent congenital anomaly * 
0 
Stillbirth with congenital anomaly 
0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing / Unknown / Lost to Follow-up 
97 80 
Not applicable 
0 
Total 
128 130 
* Pregnancy outcome categories stating no apparent congenital anomaly include outcomes where it is unknown 
whether a congenital anomaly occurred. 
Section 7.1.2.2 
Post marketing exposure in pregnant women 
Fluarix Quadrivalent: 
Overall, as of 19 February 2014 31 May 2017, GSK had received 25 64 reports of 
exposure to Fluarix Quadrivalent during pregnancy since launch on 5 August 2013. The 
outcomes of the 64 pregnancies are summarized in Table 4. 

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Table 4 
Outcomes of pregnancy exposed to Fluarix Quadrivalent 
Outcome 
Number of Cases  
since launch (n) 
Live infant, no apparent congenital anomaly * 
15 
Live infant with congenital anomaly 
0 
Elective termination, no apparent congenital anomaly * 
0 
Elective termination with congenital anomaly 
0 
Spontaneous abortion, no apparent congenital anomaly * 
1 
Spontaneous abortion with congenital anomaly 
1 
Stillbirth, no apparent congenital anomaly * 
0 
Stillbirth with congenital anomaly 
0 
Ectopic pregnancy 
0 
Molar pregnancy 
0 
Pregnancy ongoing, lost to follow-up or unknown 
47 
Total 
64 
Of the 25 pregnancy reports, 22 were ongoing at the time of reporting and 3 were 
considered lost to follow-up. 
FluLaval Quadrivalent: 
Overall, as of 17 December 2013 31 May 2017, GSK had received 5 8 reports of exposure 
to FluLaval Quadrivalent during pregnancy since launch on 15 August 2013. At the time 
of the reporting, all 5 8 pregnancies were ongoing or lost to follow-up. 
Section 7.1.3 Medical conditions for use 
The GSK sIIVs are approved by the US Food and Drug Administration (FDA) for 
prevention of disease caused by influenza A subtype viruses and type B 
viruses contained in the vaccines (Table 5). In the US, the GSK sIIVs are 
approved for use in persons 3 years of age and older or 6 months of age and older, 
depending on the vaccine. 
Section 7.2 
Rationale 
The purpose of this pregnancy registry study is to detect and describe abnormal pregnancy 
outcomes in women intentionally or unintentionally vaccinated with any of the four GSK 
sIIVs. The combination of the large number of women who are of reproductive capacity 
in the indicated age range for vaccination with GSK sIIVs, and the lack of data 
concerning vaccination during pregnancy, makes such a Registry an important 

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component of the ongoing program to assess the safety of these vaccines. This study 
is a transition of existing ongoing pregnancy registries for Fluarix, FluLaval, and 
Fluarix Quadrivalent and an ongoing PASS for FluLaval Quadrivalent into a 
combined PASS for GSK sIIVs. Timelines for collection of follow-up data will be 
adapted in order to correspond to the follow-up timelines of other GSK pregnancy 
registries. 
The Registry requires voluntary, prospective reporting of eligible pregnancies by 
patients and healthcare professionals (HCPs). Patient confidentiality is strictly 
maintained. The intent of the Registry is to prospectively collect data such as 
vaccination with any of the four GSK sIIVs during pregnancy or within 28 days 
preceding conception, potential confounding factors (such as exposure to other 
medications) and information related to the outcome of the pregnancy. 
The GSK sIIV pregnancy registry study will be maintained by GSK’s Vaccine Clinical 
Safety and Pharmacovigilance (VCSP) department. 
Section 9.1.1 Study design overview 
• 
Data collection: initial and follow-up data will be collected using 2 3 
questionnaires. Data for enrollment will be collected using the Initial 
Notification Form. Follow-up of cases is performed within 3 2 months of the 
estimated date of delivery (EDD) to ascertain pregnancy outcome (through the 
Pregnancy Outcome Form) and approximately 6 months and 12 months after the 
EDD (for all live births for whom the contact details of their HCP will be available) 
to ascertain the presence of birth defects not diagnosed before (through the 6- and 
12-month post-delivery Follow-Up Form). 
Section 9.1.2 Rationale for the study design 
This study is designed as a condition based Registry as opposed to a disease registry. 
After market authorization, adverse events (AEs) that occur after administration of the 
vaccine can and should always be reported. In that case, however, there is no clear group 
in which the events occur and so a proper rate of occurrence cannot be estimated. In this 
pregnancy registry, participants are recruited between administration of the vaccine and 
the potential occurrence of an AE (i.e., a teratogenic effect in the offspring). This allows 
for a more proper estimation of the rate of occurrence of these events. Nevertheless, the 
results of this study still need to be regarded with caution as the exact number of women 
exposed during pregnancy is unknown. Incidences of events cannot therefore be 
calculated from the study data. 
Furthermore, it is likely that pregnant women who accept vaccination may differ from 
those who refuse vaccination in underlying health status, propensity to seek medical care, 
propensity to report AEs and differences in access to medical care in general. The 
differential response/participation by vaccinated versus unvaccinated pregnant women in 
a pregnancy registry could significantly bias risk estimates and possibly in unpredictable 
ways, because of the inability to collect adequate data to characterize the non-responders. 

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Therefore, the risks of any identified birth defects will be compared to those in the 
general population, such as that defined by the Metropolitan Atlanta Congenital Defects 
Program (MACDP). 
Section 9.2.1.1 
Patient population 
In the US, the GSK sIIVs are indicated for prevention of disease caused by influenza A 
subtype viruses and type B viruses contained in the vaccine. GSK sIIVs are approved for 
use in persons 3 years of age and older or 6 months of age and older, depending on the 
vaccine. 
The study population includes women vaccinated with any of the four GSK sIIVs 
during pregnancy or within 28 days preceding conception. 
Section 9.2.1.2 
Potential annual exposure 
Number of pregnant vaccinees 
The four GSK sIIVs are classified as Pregnancy Category B. Although the number of 
pregnant women who will be vaccinated with GSK sIIV with this registry is impossible to 
predict, experiences with other vaccine pregnancy registries (e.g., smallpox vaccine 
[CDC, 2003], varicella vaccine [Shields, 2001] and Twinrix) indicate that it is likely that 
fewer than 100 pregnancies per year will be registered for each of the vaccines. 
Section 9.2.2 Patient recruitment 
Reporting of vaccine-exposed pregnancies to the Registry is voluntary. Reporters 
become aware of the Registry through the US Prescribing Information (PI) and in the 
case of healthcare providers the GSK Registry website. The PIs for each of the sIIVs and 
GSK registry website each give a brief summary of the purpose and intent of the Registry, 
along with telephone and fax contact information. The forms for enrolling and 
reporting outcomes are also accessible to healthcare providers through the GSK 
Registry website. Additionally, GSK has requested that information regarding GSK 
pregnancy registries be posted directly on the FDA website. 
Section 9.2.5 Inclusion criteria 
A subject will be included in the Registry if all of the following criteria are met: 
• 
Exposure to GSK sIIVs occurs during pregnancy or within 28 days preceding 
conception. 
• 
Subject is a US resident. 
• 
A HCP is identified (name, address and phone number). 
• 
Subject can be identified (by GSK or HCP). 

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Data from registered subjects will be included in the analyses if the following criterion is 
met: 
• 
Pregnancy is ongoing and the outcome is unknown at the time of initial report. 
Section 9.2.6 Exclusion criteria 
Data from registered subjects will not be included in the analyses if the following 
criterion is met: 
• 
Outcome of pregnancy is known at the time of initial report. Types of known 
outcomes include prenatal testing reports in which the results are abnormal or 
outside the reference range, indicating possible abnormality in the fetus. Pregnancies 
in which prenatal testing indicates a normal pregnancy would also be excluded 
because inclusion of such pregnancies could potentially bias results toward a lower 
overall estimate of risk for defects [Honein, 1999]. Typically pregnancies > 16 weeks 
gestation will have undergone prenatal testing that can identify whether a child has 
congenital abnormalities. 
Section 9.3.2 Data to be collected 
Data will be collected using 2 3 questionnaires; one for enrollment (i.e. Initial 
Notification Form) initial data and, one for follow-up data after the EDD (i.e. 
Pregnancy Outcome Form) and one for infant data at about 6 and 12 months after 
EDD (i.e. 6- and 12-month post-delivery Follow-Up Form. 
With the information gathered from these questionnaires, the frequency of birth 
defects among enrolled subjects will be calculated and individual reports will be 
evaluated for causal assessments, if possible. 
Section 9.3.2.1 
Questionnaire for initial data collection 
The following initial data will be collected using the questionnaire for initial data 
collection (i.e. Initial Notification Form): 
• 
Patient identifier. 
• 
Maternal medical and family history including date of birth, date of last 
menstrual period (LMP), EDD, ethnicity. 
• 
Type of conception. 
• 
Prenatal testing. 
• 
Number and outcome of previous pregnancies, including details of birth defects if 
applicable. 
• 
Maternal/paternal history which may have an impact on the outcome of this 
pregnancy. 

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• 
Fluarix, FluLaval, Fluarix Quadrivalent or FluLaval Quadrivalent vaccination 
including lot number and date of administration. 
• 
Other drug/vaccine exposure including drug/vaccine name, route of administration, 
dose, lot number, indication and date of administration. 
• 
Occurrence of AEs (if any), including onset/end date, outcome and relationship to 
GSK products. 
• 
Name of HCP name supervising pregnancy and contact information, if available. 
• 
Any additional data that seems relevant for this study.] 
Section 9.3.2.2 
Questionnaire for follow-up pregnancy outcome data collection 
The following follow-up data will be collected using the questionnaire for follow-up 
pregnancy outcome data collection (i.e. Pregnancy Outcome Form): 
• 
Pregnancy outcome. 
• 
Method of delivery. 
• 
Fetal/neonatal status, including description of birth defects if applicable. 
• 
Infant information including gestational weeks at birth/miscarriage/termination, 
gender, length, weight, Apgar score. 
• 
Additional drug/vaccine exposure including drug/vaccine name, route of 
administration, dose, lot number, indication and date of administration. 
• 
AEs experienced by the fetus/infant or the mother. 
• 
Name of the HCP name supervising the infant and contact information. 
• 
Any additional data that seems relevant for this study. 
Section 9.3.2.3 
Questionnaire for infant data collection 
The following data on the infant will be collected using the questionnaire for 6- and 
12-month after delivery follow-up data collection (i.e. 6 and 12-month post-delivery 
Follow-Up Form): 
• 
Infant status, including description of birth defects not diagnosed at the time of 
the initial follow-up, if applicable. 
• 
AEs experienced by the infant. 
• 
Additional drug/vaccine exposure including drug/vaccine name, route of 
administration, dose, lot number, indication and date of administration. 
• 
Any additional data that seems relevant for this study. 
Section 9.4 
Data sources 

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Reporting of vaccine-exposed pregnancies to the Registry is voluntary. Registration 
can be initiated from a HCP or from a consumer; in the latter case permission is 
requested to obtain confirmation and follow-up from their HCP. Registration can be 
initiated from a HCP, their staff or from a consumer. Permission from consumers 
is requested to obtain confirmation and follow-up from their HCP, as well as 
follow-up from the HCP participating in the care of the infant. A toll-free telephone 
number for reporting AEs and vaccine-exposed pregnancies to the Registry are listed 
in the product information leaflets and on the GSK Registry website. Retrospective post-
marketing reports and relevant scientific publications are potential sources of additional 
information. 
Section 9.5 
Study size 
No minimum sample size is required for this descriptive registry study. 
Refer to Section 9.2.1.2 for the size of the potential “at-risk” population and the 
number of pregnant vaccinees. 
Section 9.6.1 Data collection 
Initial and follow-up data will be collected using 2 3 questionnaires. Initial data will be 
collected before the outcome is known. Follow-up of cases is performed at the 
following timepoints:, with each follow-up independent from the others: 
For consumer reports: 
• 
At initial notification of pregnancy exposure: 2 attempts at 4-6 week intervals 
will be made to obtain more information about the pregnancy (e.g. estimated 
time of delivery (EDD) and/or last menstrual period (LMP) and to obtain 
permission to contact the patient’s HCP 
• 
Within 2 months after EDD, 1 additional attempt is made, if permission to 
contact the patient’s HCP has not already been granted, to obtain more 
information about the pregnancy and obtain the permission to contact the 
patient’s HCP. 
For HCP reports: 
• 
At initial notification of pregnancy exposure or once permission has been 
granted for reports initially received from a consumer, 2 attempts at 4-6 week 
intervals will be made to obtain more information via pregnancy follow-up 
form. If the HCP submitting the report (or his/her staff) participating in the 
care of the pregnant female, reports will only be processed if contact 
information for the relevant HCP supervising the pregnancy is provided 
and/or if permission has been granted by the mother. 

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• 
Within 3 2 months of the EDD, to ascertain outcome. At least three Two 
attempts to obtain outcome information will be made before any case is 
considered lost to follow-up. 
• 
An additional follow-up will be done for all live births (as confirmed around EDD) 
approximately 6 months after the EDD to ascertain the presence of birth defects not 
diagnosed at the time of the initial follow-up. 
• 
The last follow-up will be done for all live births (as confirmed around EDD) at 
approximately 12 months after the EDD to ascertain the presence of birth defects not 
diagnosed at previous follow-ups. 
Section 9.6.2 Processing of reports 
Initial rReports are entered into the GSK safety database by Client Response Center 
staff GSK Case management group responsible for all case entry into GSK’s 
worldwide safety database using existing mechanisms and practices. Follow-up is 
conducted by the Case Management Group. The HCP supervising the pregnancy is 
contacted if she/he requests or if initial information is insufficient or needs 
clarification. The HCP supervising the health of the infant (and/or their staff) is 
contacted for all live births and if permission has been granted by the mother. The 
HCP is encouraged to keep a copy of the initial completed form in the patient’s chart. 
Section 9.6.2.1 
Solicitation of outcome 
As explained in section 9.6.1, within three two months after the EDD and if the HCP has 
not already provided the outcome, she/he is sent an a pregnancy outcome form 
(questionnaire), along with a copy of the initial completed pregnancy form. The 
mode of communication is the one through which the initial information was 
received (telephone, fax, or postal mail) generally via a standard letter. 
At least three Two attempts are made to secure the outcome information from the HCP. 
The second and third attempt also utilizes standard letter as mode all modes of contact 
available (mail, fax, telephone). If outcome is not received from the HCP and contact 
information is available for the patient, she is then contacted by mail or fax.In the 
event of an abnormal outcome For all live births (as confirmed around EDD) and 
with the mother’s permission, attempts are made to solicit information from the 
pediatrician and/or other specialists who have provided healthcare/consultation to the 
child up until 12 months of age. 
Section 9.7 
Data analysis 
Pregnancy outcomes include spontaneous abortion (pregnancy loss before 20 22 weeks 
gestation), fetal deaths/stillbirths (loss at or after 20 22 weeks gestation), 
elective/therapeutic abortions and live births. Gestational weeks are counted from the 
date of the LMP. The second trimester is considered to begin at week 14 and the third 

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trimester begins at week 28. The presence or absence of birth defects or other 
abnormalities is evaluated within each of the preceding outcome categories. 
Pregnancy outcomes are stratified by the trimester of exposure, with an additional 
stratum for preconception exposure with no subsequent administration of vaccine during 
pregnancy. Receiving multiple administrations of GSK sIIV during a single pregnancy 
is unlikely; however, if this does occur, reports of multiple exposures during a 
pregnancy are classified by the earliest trimester of exposure.  
The calculations of risk for birth defects are made by dividing the number of infants with 
birth defects by the total number of infants with and without birth defects. Since the 
presence of birth defects will be assessed around EDD and at approximately 6 and 12 
months after the EDD (for all live births), the calculation of risk will be performed for 
two separate cohorts: 1). the risk of birth defects for all subjects who completed the 
outcome form at around EDD (regardless of whether they were lost-to-follow up 
afterwards) and 2). the risk of birth defects for all subjects reporting live births and 
who completed either or both the 6- and 12-month post-delivery follow-up forms. 
The outcomes of the study will be assessed against known rates from an external 
reference group for the likelihood of a safety signal warranting further investigation. In 
each periodic and the final reports, the data will be analyzed for all GSK sIIVs pooled 
and for each of the 4 vaccines separately. The analyses will also include data collected 
cumulatively in each individual registry up to the initiation of the combined Registry for 
GSK sIIVs. Individual reports of birth defects following vaccination with any of the 
GSK sIIVs will also be evaluated for causal assessments, as appropriate. 
The majority of spontaneous abortions occur early in pregnancy [Wilcox, 1981; 
Wilcox, 1983; Ellish, 1996]. If spontaneous abortions were to be evaluated as an 
outcome of interest, it would be essential to enroll pregnancies as soon as possible after 
vaccination with GSK sIIV. Because enrollment and recognition of pregnancy would 
occur at various times, it would be virtually impossible to meaningfully evaluate the 
effects of GSK sIIV on pregnancy loss [Kennedy, 2004]. Therefore, spontaneous 
abortions without birth defects are excluded from the risk calculations. 
The risk in the general population of all birth defects meeting CDC criteria is 
approximately 3% (1 of 33) of live births [CDC, 2013]. The estimated risk cited in the 
medical literature varies because of differences in case definitions, populations sampled 
and ascertainment methods. The Collaborative Prenatal Project, using a broader case 
definition and prospective ascertainment, reports a frequency of 5% to 7% [Chung, 
1975]. Most major structural defects originate during the first trimester of pregnancy, 
which is the critical time for organogenesis [Niebyl, 2012]. For such defects, exposures 
occurring in the second or third trimester are not likely to be causally associated. 
However, for the sake of completeness and to enable the assessment of possible increases 
in the frequency of birth defects, all defects will be included in the periodic summary 
reports of this Registry and stratified by trimester of exposure. 

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Criteria for review of a specific individual report include: 
• 
Is the timing of the vaccination with GSK sIIVs commensurate with the 
ontogenetic development of the organ(s) affected by the abnormalities? 
• 
Is there another known or likely cause (e.g., pre-existing genetic or chromosomal 
defect or exposure to a known teratogen)? 
• 
Is the congenital abnormality not previously described (i.e., is it new to medical 
science)? 
• 
Is there a unique constellation of defects (i.e., is there a new syndrome)? 
Criteria for review of aggregate data include: 
• 
Is there a deviation from the expected frequency of all defects indicating an 
increase in the overall risk of defects? 
• 
Is there a deviation from the expected frequencies of individual defects? 
• 
Is there uniqueness (e.g., a pattern) of the abnormalities that is suggestive of a common 
etiology? 
Studies have shown the risk of spontaneous abortion is high early in pregnancy and 
decreases substantially from week 8 to week 28, yielding a cumulative estimated risk of 
10% to 22% [Wilcox, 1981; Wilcox, 1983; Wilcox, 1988; Fenster, 1997; Windham, 
1997; Khattak, 1999; Anderson, 2000; Osborn, 2000]. 
While the Registry is to be limited to prospective reports, some pregnancy exposures are 
reported after pregnancy outcome has been identified (retrospective reports). The 
Registry will capture retrospective reports, but these reports will not be included in the 
analyses of prospective reports. In general, retrospective notification of outcomes 
following exposure to drugs or vaccines is biased toward reporting the severe and 
unusual cases and is not reflective of the general experience with the drug. Information 
about the total number of exposed pregnancies, i.e., the pool of exposures from which the 
retrospective reports arise, is unknown; therefore, incidences of outcomes cannot be 
calculated from these data. A series of reported birth defects, however, can be analyzed to 
detect patterns of specific congenital abnormalities and can identify early signals of new 
vaccine-associated risks. A section of each periodic summary report, separate from the 
analysis of prospective reports, will describe all abnormal outcomes of retrospectively 
reported cases. 
Section 9.9 
Limitations of the research methods 
This Registry is a prospective cohort study convenience sample of pregnant women 
who are followed prospectively. Active enrollment of a valid internal comparison 
group is not possible. Therefore, background risks from existing, external systems 
(e.g., the National Birth Defects Prevention Network and the National Center for Health 
Statistics) are used. The potential limitations of comparisons between Registry and 
background data depends upon the event(s) being compared and will be discussed on an 
ad hoc basis in the relevant periodic Registry reports. In addition, variations in the 

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year-to-year (or strain), resulting in differences in the safety profiles of the vaccines, 
remain a possible limitation. 
Refer to Section 9.1.2 for other potential limitations of the study. 

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ANNEX 5 Trademarks 
The following trademarks are used in the present study outline. Note: In the remainder of 
the document, the names of the vaccines will be written without the superscript symbol 
™ or ®. 
Trademarks of the GSK group of 
companies 
 
Generic description 
Fluarix® 
 
trivalent inactivated influenza virus vaccine 
Fluarix® Quadrivalent 
 
quadrivalent inactivated influenza virus 
vaccine 
FluLaval® 
 
trivalent inactivated influenza virus vaccine 
FluLaval® Quadrivalent 
 
quadrivalent inactivated influenza virus 
vaccine 
Twinrix® 
 
hepatitis A inactivated & hepatitis B 
(recombinant) vaccine 

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ANNEX 6 Protocol Amendment 1 sponsor signatory approval 
eTrack study number and 
Abbreviated Title 
201476 (EPI-FLU-039 VS US PR) 
Date of protocol 
Amendment 1 Final: 27 October 2017 
Detailed Title 
Fluarix®/ FluLaval®/ Fluarix® Quadrivalent/ 
FluLaval® Quadrivalent Pregnancy Registry: a 
prospective, exploratory, cohort study to detect and 
describe abnormal pregnancy outcomes in women 
intentionally or unintentionally vaccinated with 
Fluarix® or Fluarix® Quadrivalent or FluLaval® or 
FluLaval® Quadrivalent during pregnancy or within 
28 days preceding conception. 
Sponsor signatory 
Anne Yeakey,  
Head, Safety Evaluation & Risk Management, 
Vaccine Clinical Safety and Pharmacovigilance 
 
 
Signature 
 
 
 
Date