COHORT STUDY OF VENOUS THROMBOEMBOLISM AND OTHER CLINICAL ENDPOINTS AMONG OSTEOPOROTIC WOMEN PRESCRIBED BAZEDOXIFENE, BISPHOSPHONATES OR RALOXIFENE IN EUROPE
Conditions: Osteoporosis, Postmenopausal
Sponsor: Pfizer

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NON-INTERVENTIONAL (NI) DRUG STUDY PROTOCOL
COHORT STUDY OF VENOUS THROMBOEMBOLISM AND OTHER CLINICAL 
ENDPOINTS AMONG OSTEOPOROTIC WOMEN PRESCRIBED 
BAZEDOXIFENE, BISPHOSPHONATES OR RALOXIFENE IN EUROPE
Compound Number:
PF-05208749
Compound Name:
Bazedoxifene
Study Number:
B1781044
Version and Date:
Final
Amendment III
19 August 2013

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TABLE OF CONTENTS
1. INTRODUCTION .......................................................................................................................4
1.1. Background and Rationale ..............................................................................................4
2. STUDY OBJECTIVES AND ENDPOINTS...............................................................................5
2.1.1. Primary Objective...............................................................................................5
2.1.2. Secondary Objective...........................................................................................5
2.2. Endpoints.........................................................................................................................5
2.2.1. Primary endpoints:..............................................................................................5
2.2.2. Secondary endpoints:..........................................................................................5
3. STUDY DESIGN.........................................................................................................................6
3.1. Data Source .....................................................................................................................6
3.2. Contents of the Cegedim LPD ........................................................................................7
4. STUDY POPULATION..............................................................................................................8
4.1. Inclusion Criteria.............................................................................................................8
4.2. Subject Accrual Period....................................................................................................9
5. STUDY TREATMENT AND DURATION ...............................................................................9
6. STUDY PROCEDURES .............................................................................................................9
6.1. Follow up time and drug exposure time..........................................................................9
6.1.1. Follow up:...........................................................................................................9
6.1.2. Drug exposure:....................................................................................................9
6.2. Study Period ..................................................................................................................10
6.3. Endpoint identification..................................................................................................10
7. DATA ANALYSIS/STATISTICAL METHODS.....................................................................11
7.1. Sample Size Calculation................................................................................................11
7.2. Safety Analysis..............................................................................................................12
7.3. Interim Analysis ............................................................................................................13
8. DATA COLLECTION AND DATA MANAGEMENT...........................................................13
8.1. Case Report Forms/Electronic Data Record .................................................................13
8.2. Record Retention...........................................................................................................14
9. ADVERSE EVENT REPORTING AND SERIOUS ADVERSE EVENT 
REPORTING .......................................................................................................................14
10. POTENTIAL WEAKNESSES................................................................................................15

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11. ETHICS....................................................................................................................................16
11.1. Institutional Review Board (IRB)/Ethics Committee (EC).........................................16
11.2. Ethical Conduct of the Study ......................................................................................16
11.3. Subject Information and Consent................................................................................16
12. COMMUNICATION AND PUBLICATION OF STUDY RESULTS...................................16
12.1. Communication of results by Pfizer............................................................................16
13. REFERENCES ........................................................................................................................17

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1. INTRODUCTION
1.1. Background and Rationale
Osteoporosis is characterized by a decrease in bone mass and architectural deterioration of 
bone tissue. Subtle modifications of bone remodeling, related to abnormalities of bone 
turnover, can induce a substantial loss of bone over a prolonged period of time. A period of 
asymptomatic bone loss results in reduced bone strength. When bone loss is sufficient to 
cause mechanical weakness, fractures may occur spontaneously or as a result of minimal 
trauma. Osteoporotic fractures cause substantial clinical and economic burden for society. 
Age and menopause are the two main determinants of osteoporosis. The cessation of ovarian 
production of estrogen, at the time of the menopause, results in an accelerated rate of bone 
loss in women.
Bazedoxifene (BZA) is a third generation non-steroidal selective estrogen receptor modulator 
(SERM) currently approved in the European Union (EU) for the treatment of postmenopausal 
osteoporosis in women at increased risk of fracture. BZA is an estrogen receptor ligand that 
exhibits tissue specific activity: BZA functions as an agonist in the bone and an antagonist in 
the breast and uterine endometrium. BZA was developed in tablet form and current dosing 
consists of once daily administration of a 20 mg tablet. BZA (Conbriza) was approved in 
Europe via the centralized authorization procedure in April 2009. The first EU launch 
occurred in Spain in September 2010 which will be followed by launch in Italy in April 
2011. 
Currently, one other SERM, raloxifene (Evista®) is marketed in Europe for the treatment and 
prevention of postmenopausal osteoporosis. Bisphosphonates are non-hormone compounds 
that bind to the bone surface and are then taken up by osteoclasts.  Bisphosphonates have a 
profound effect on bone remodeling, and are widely used for the prevention and treatment of 
osteoporosis.
In clinical trials, BZA-treated women had an increased risk of venous thromboembolic 
events (VTEs) compared to placebo. VTEs are included in the product label as an important 
identified risk.
This observational cohort study is being conducted to further characterize selected adverse 
events of interest among a patient population prescribed bazedoxifene, raloxifene, or a 
bisphosphonate in usual clinical care outside of a randomized clinical trial setting. This post-
authorization safety study (PASS) is a post-authorization commitment to the CHMP/EMA.
The product Summary of Product Characteristics (SmPC) will be used as the single reference 
safety document for expedited safety reporting purposes for this study.

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2. STUDY OBJECTIVES AND ENDPOINTS
2.1.1. Primary Objective
To estimate and compare the incidence rates of venous thromboembolism (VTE) among 
women receiving bazedoxifene and women receiving a bisphosphonate for treatment of 
osteoporosis.
2.1.2. Secondary Objective
To estimate and compare the incidence rates of VTE among women receiving bazedoxifene 
and women receiving raloxifene for treatment of osteoporosis.
To estimate and compare the incidence rates of selected clinical endpoints (listed as 
secondary endpoints in section “2.2 Endpoints”) among women receiving bazedoxifene and
women receiving a bisphosphonate for treatment of osteoporosis.
To estimate and compare the incidence rates of selected clinical endpoints (listed as 
secondary endpoints in section “2.2 Endpoints”) among women receiving bazedoxifene and 
women receiving raloxifene for treatment of osteoporosis.
2.2. Endpoints
The clinical endpoints for this study were determined based on the clinical and pre-clinical 
data from the bazedoxifene development program, class effects of other SERMs, and 
recommendations of the EU Rapporteurs.
Potential endpoints will be identified by an electronic search of the coded diagnosis fields of 
the medical records. The relevant diagnostic codes that will be used as operational definitions 
of each of the endpoints will be listed in the statistical analytic plan of the study. The 
available medical record of the identified cases for the primary endpoint will be retrieved and 
reviewed to confirm the diagnosis.
2.2.1. Primary endpoints: 

Venous thromboembolism (VTE) defined as deep vein thrombosis (DVT), pulmonary 
embolism (PE), retinal vein thrombosis, and sinus thrombosis 
2.2.2. Secondary endpoints:

Ischemic stroke

Thrombotic and ischemic cardiac disorders (including myocardial infarction, 
myocardial ischemia, and coronary occlusion)

Atrial fibrillation

Biliary events: cholecystitis, cholelithiasis

Hypertriglyceridemia 

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
Fractures

Chronic and acute renal failure (including chronic renal insufficiency and end stage 
renal disease)

Malignancies including breast, renal, ovarian, thyroid, gastrointestinal tract and lung 
cancers, as well as an aggregate of all malignancies

Depression

Selected ocular events including retinal vascular occlusions, disorders of the globe, 
iris, ciliary body, retina, eye adnexa and cornea.

Goitre
3. STUDY DESIGN
This post-authorization safety study (PASS) is an observational, non-interventional 
epidemiologic cohort study using data from a European database of electronic medical 
records. 
3.1. Data Source
This study will use the Cegedim Longitudinal Patient Database (LPD), an electronic medical 
records database that collects clinical data from primary care physician practices in the 
following European countries i.e., Spain, Italy, Germany, France, Belgium and UK. (In the 
UK the database is known as The Health Improvement Network (THIN).) For this study the 
Cegedim LPD in Italy and Spain will be used. If during the recruitment period of the study 
bazedoxifene is launched in other European countries where Cegedim LPD is available, the 
study may be expanded to include those countries. 
The Cegedim LPD obtains medical information from a proprietary practice management 
software used during physician office visits to capture clinical data in an electronic medical 
record system. Physicians use the practice management software developed by Cegedim to 
maintain electronic medical records of their patients. In each country a panel of physicians 
using this electronic system volunteered to make available anonymized patient-level 
information from their practices for clinical research purposes. Since these data are being 
collected in usual clinical care in a non-interventional way, they reflect routine clinical 
practice in these countries. The panel of contributing physicians is maintained as a 
representative sample of the primary care physician population in each country according to 
age, sex, and geographical distribution. Additionally in most countries, the patient population 
is representative of the respective country population according to age and sex distribution, 
as provided by national statistic authorities.  

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Table 1: Doctor and patient populations in the Cegedim LPD by country
France
UK
Italy
Germany
Spain
Number of physicians in the
panel
1200
1200
700
550
300
Average number of patients who 
consulted GP at least once in a year
1,600,000
1,400,000
800,000
680,000
320,000
The patient data in the LPD form a nationally representative sample. Data have been 
collected in Italy since 2004 and in Spain since 2006, providing several years of medical 
history, including comorbidity and concomitant medication use information.  Of the patients 
included in the Spanish and Italian LPD, there are currently approximately 68,000 women 
with drug-treated osteoporosis.  Between 1 and 6% of these patients are taking raloxifene, 
depending on the region; most of the rest are prescribed a bisphosphonate (Cegedim, data on 
file).
3.2. Contents of the Cegedim LPD
Data are entered regularly during usual patient care, submitted daily to the Cegedim 
coordinating center, cleaned and de-identified, and then made available for research. 
Anonymized patient data collected from each GP practice includes:
·
Demographic information (age, gender)
·
Medical history (event dates, diagnoses, risk factors, referrals to specialists)
·
Therapeutic history (date/length of prescription, molecule/product, dosage)
·
Additional information (test results, immunizations, height, weight, blood pressure)
Patient data collected by Cegedim in each country participating in the LPD varies to some 
extent to accommodate local needs. However, all countries collect data on medical 
comorbidities and outcomes, prescriptions, demographics, and physician characteristics.  
In the Cegedim electronic medical record system diagnosis of clinical events are recorded as 
diagnostic codes. These codes from the different participating countries will be harmonized 
based on prespecified algorithms developed prior to the analysis and listed in the statistical 
analytic plan. 

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Table 2: Data coding conventions in the different countries
France
UK
Italy
Germany
Spain
Drug code
dictionary
Claude Bernard
Multilex
Farmadati
Abdata
Vademecum
Therapy
classification
European 
Pharmaceutical 
Marketing 
Research 
Association 
(EphMRA)
British 
National 
Formulary 
(BNF)
Anatomical 
Therpeutic 
Chemical 
(ATC)
ATC
ATC
Disease
classification
Home grown
thesaurus
mapped to 
International 
Classification of 
Diseases-10 
(ICD-
10) and
International 
Classification of 
Primary Care-2 
(ICPC-2)
Read
Codes
ICD-9
ICD-10
Code CIAP
mapped to
ICD-9
Cegedim LPD does not collect hospitalization data directly except in the UK THIN database.  
Information on hospitalizations is captured in the patient’s general practice file during 
follow-up visits with the patient’s general practice physician following discharge from the
hospital. However, this information is not systematically collected and there is no established 
linkage between the medical records at the general practices and at the hospitals. 
4. STUDY POPULATION
All women in the Cegedim database meeting the inclusion criteria will be included in the 
analysis without any sampling process. 
4.1. Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for inclusion into the 
study:

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1. Female
2. At least one prescription for bazedoxifene, raloxifene, or any bisphosphonate during the 
study inclusion period (index prescription); 
3. A recoded diagnosis code of osteoporosis on or within 60 days prior to the index 
prescription date;
4. Age >=45 at the date of the index prescription; and 
5. At least 6-months of follow-up data in the electronic medical record system prior to the 
date of the index prescription
4.2. Subject Accrual Period
The study will operationally launch after bazedoxifene becomes commercially available in 
the participating countries. However, the subject inclusion period in the database will begin 
at the time of the commercial launch of bazedoxifene in each country (e.g., September 2010 
in Spain, April 2011 in Italy) and will continue for three (3) years from the start of the study.
5. STUDY TREATMENT AND DURATION
This study involves retrospective analysis of prospectively collected data in an existing 
electronic database for the purpose of usual clinical care. It is expected that osteoporosis 
medications will be used on the basis of the approved SmPCs and will be adjusted solely 
according to medical and therapeutic necessity. As this is a non-interventional study there is 
no study mandated dosing regimen or visit schedule. Physicians will be prescribing the drugs 
according to the standard clinical practice in the participating countries. There is no study 
mandated duration of therapy. 
6. STUDY PROCEDURES 
6.1. Follow up time and drug exposure time
6.1.1. Follow up: 
Each woman will be followed for identification of the selected endpoints for a period of up to 
five years from the date of the index prescription record for bazedoxifene, raloxifene or a 
bisphosphonate. The follow up will continue even if the woman discontinues the index 
medication or switches to a different medication during the five year period. 
The follow up duration of an individual woman may be shorter than the five year period if 
the woman transfers out of her GP office that wrote the index prescription, or if the database 
records the death of the woman. In these situations the data will be censored on the date of 
transfer or the date of death. 
6.1.2. Drug exposure: 
Exposure to the drugs under study will be ascertained by searching the prescription records 
for the relevant product codes. For each prescription the duration of exposure will be 

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estimated based on the dose and quantity of the prescribed medication. For each prescription, 
person-time exposed to the drug will begin to accrue from the date of the prescription. The 
follow up time will be categorized into:

Current exposure: defined as the duration of the prescription

Recent exposure: defined as the 60-day period following the end of the duration of 
prescription

Past exposure: defined as any follow up time accrued after 60 days following the end 
of the duration of the prescription.
A sensitivity analysis will be conducted with a different definition of exposure categories 
(e.g., using a 90-day window to define recent exposure). 
Given the discontinuous nature of osteoporosis medication use, it is likely that a large 
number of women in this study will accrue ‘current use’, ‘recent use’ and ‘past use’ exposure 
time to multiple osteoporosis drugs during the 5-year period of follow up. 
Drug exposure will also be categorized with respect to the cumulative exposure to each drug 
(e.g., 0-days, 1-30-days, 31-90-days, 91-180-days, 181-365-days, >365-days) to evaluate 
whether or not the incidence (hazard) of a specific adverse event varies with increased 
duration of use.  
6.2. Study Period
It is expected that this study will take at least nine (9) years to complete, with a 3 year subject 
accrual period, 5 years of follow-up per patient and 1 year for data cleaning, analysis and 
report generation. Depending on the rate of uptake of bazedoxifene in the participating 
countries the accrual period may need to be extended to ensure adequate sample size. The 
patient accrual data will be reviewed annually to determine whether the uptake is sufficient to 
complete the study in the proposed time period.
6.3. Endpoint identification
The relevant diagnostic codes for each of the endpoints will be specified in the statistical 
analytic plan. Endpoints will be identified based on an electronic search for the relevant 
diagnostic codes in the diagnosis fields of the medical records during the follow up period.  
For the identified potential cases, the electronic medical record will be retrieved and 
reviewed by a clinical expert to confirm the diagnosis for the following endpoints:
The primary endpoint:
a.
Venous thromboembolism (VTE) defined as deep vein thrombosis (DVT), 
pulmonary embolism (PE), retinal vein thrombosis, and sinus thrombosis.
Secondary endpoints

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b. Ischemic stroke
c.
Thrombotic and ischemic cardiac disorders (including myocardial infarction, 
myocardial ischemia, and coronary occlusion; and includes both acute and 
chronic disorders).  
d. Malignancies: Breast, ovarian, renal, thyroid and endometrial.
e.
Any ocular event with a vascular etiology (possibly indicative of retinal vein 
thrombosis, e.g. retinal arterial thrombosis, retinal hemorrhage, visual field 
defects of vascular origin).
7. DATA ANALYSIS/STATISTICAL METHODS
The details of the data analysis will be documented in a Statistical Analysis Plan (SAP) 
document, which will be maintained by the sponsor.  The SAP will elaborate, and may 
modify the analytic plans outlined in the protocol; however, any major modifications will be 
reflected in a protocol amendment.
7.1. Sample Size Calculation
There is no active de novo patient enrollment in this study and all women in the database 
who meet the inclusion criteria during the recruitment period will be included in the analysis. 
Therefore, the focus of the sample size calculation was to determine the precision of the 
estimated incidence rate ratios (IRR) that can potentially be achieved in the study depending 
on several different hypothetical scenarios of subject accrual. Depending on drug uptake in 
the participating countries, speed of accrual, event rates, and actual dropout rates, the 
precision of the estimated incidence rate ratio may change.
The estimates are based on the expected incidence rate of VTE as the primary endpoint.  It is 
estimated that the incidence rate of VTE in women who are not treated with a SERM or HT 
is 1.74/1000 patient-years (PY), based on data from the placebo groups in bazedoxifene 
clinical trials. It is assumed that women treated with raloxifene would have a higher 
incidence of VTE, of 2.17/1000 PY, based on data from the Phase III pivotal trials of 
bazedoxifene.  The rate of VTE observed in the raloxifene arm of the bazedoxifene pivotal 
trials is lower than the rate reported in the Multiple Outcomes of Raloxifene Evaluation 
(MORE) trial [1]. In the MORE trial, the incidence rate of VTE was 3.5/1000 patient-years in 
women randomized to raloxifene. Therefore, our calculations are likely to be substantially 
more conservative than estimates based on rates in the literature.
All estimates (Table 3, Table 4) were calculated with two-sided 95% confidence intervals.  
According to the study plan, there will be a 3-year accrual period and each woman will be 
followed for up to 5 years from enrollment. Since osteoporosis therapies are chronic 
therapies, it is likely that women will be exposed to the drugs for more than one year. A 
conservative annual loss to follow up rate of 15% was used in the estimation.  Estimates were 
based on Wald 95% confidence intervals [2]

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Table 3: 95% Confidence Intervals (CI) for Incidence Rate Ratios (IRR) with different 
numbers of patients in the BZA arm and the primary comparator arm
Bazedoxifene
Bisphosphonate
BZA:Bisphosphonate
Underlying Incidence Rate 
Ratio (IRR)
(n)
(n)
1
1.5
2
95% CI of observed point 
estimate of IRR
2150
8600
1:4
0.6, 1.7
1.0, 2.4
1.3, 3.0
2000
8000
1:4
0.6, 1.8
0.9, 2.4
1.3, 3.1
1750
10,500
1:6
0.6, 1.8
0.9, 2.5
1.3, 3.1
1500
12,000
1:8
0.5, 1.9
0.9, 2.5
1.3, 3.2
The estimated 95% CI of the incidence rate ratios (IRR) in Table 3 imply that if the 
underlying (true) IRR comparing BZA users to bisphosphonate users is 2, then the point 
estimate of IRR in the study will lie between 1.3  and 3.2 indicating (a) that the study will be 
able to rule out equality of the IRRs (i.e., IRR>1) and (b) that the study would not be able to 
rule out the possibility that the true IRR could be as high as 3.2 or as low as 1.3.
Table 4: 95% Confidence Intervals (CI) for Incidence Rate Ratios (IRR) comparing 
BZA users and Raloxifene users assuming equal number of patients in the two arms
Bazedoxifene
Raloxifene
BZA:Raloxifene
Incidence Rate Ratio (IRR)
(n)
(n)
1
1.5
2
95% CI of observed point 
estimate of IRR
2150
2150
1:1
0.5, 1.9
0.9, 2.7
1.2, 3.4
The estimated 95% CI of the incidence rate ratio (IRR) in table 4 implies that if the 
underlying (true) IRR comparing BZA users to raloxifene users is 2, then the point estimate 
of IRR in the study will lie between 1.2  and 3.4 indicating (a) that the study will be able to 
rule out equality of the IRRs (i.e., IRR>1) and (b) that the study would not be able to rule out 
the possibility that the true IRR could be as high as 3.4 or as low as 1.2.
7.2. Safety Analysis
Descriptive statistics on available patient characteristics (e.g., age, BMI, smoking and alcohol 
use, history of relevant medical diagnoses, use of relevant concomitant medications) will be 
reported for all exposure groups at baseline.
Incident cases of study endpoints will be included in the analysis. Women with a history of 
study outcomes recorded in the medical records prior to the index prescription will not be 
included in the primary analysis for that specific outcome, but will be analyzed separately. 
For example, a woman with a history of VTE prior to the index prescription will be 
categorized as a prevalent case and will be excluded from the primary VTE analysis. A 

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separate analysis for women with a medical history of VTE will be performed and the 
woman would remain eligible for the analysis of other outcomes as normal. Depending on 
the number of patients in these subgroups of prevalent cases of each endpoint, this 
supplemental analysis is likely to have low power to perform any statistical comparison and 
will be descriptive in nature. 
Incidence rates will be calculated for all endpoints in all treatment groups; incidence rate 
ratios and 95% confidence intervals will be calculated and compared. Stratifications by risk 
factors of interest (e.g., age, BMI, history of selected medical comorbidities, selected 
concomitant medications) will be performed for each outcome depending on availability of 
the data. A multiple regression model may be fit for the primary objective of the study 
depending on the completeness of the data on potential confounders and accrual of a 
sufficient number of endpoints. 
A time to event analysis may be conducted as a secondary analysis.
All analyses will be conducted for each country separately, as well as after pooling the data 
from all participating countries. 
Given the rarity of certain malignancies in this population, the incidence rates observed in 
this study may be small and imprecise. In such case, to better characterize the rates obtained 
in this study, an additional analysis using external reference data for the malignancies may be 
conducted. The observed frequency of malignancies in all three treatment groups will be 
compared with the expected frequency calculated from an age and gender matched 
population-based reference group (e.g., GloboCan)  This ratio of observed versus expected 
events and 95% confidence interval, will be reported.
7.3. Interim Analysis
An interim analysis will be conducted once, after four (4)years of study data become 
available.
This interim analysis will include a calculation of crude event rates for the study outcomes in 
each exposure group. The observed rates of the primary endpoint will be used to determine if 
the rates are sufficient to continue the study as planned. Based on the results of this interim 
analysis, the study may be extended in order to accrue the number of events required to 
preserve the precision of the incidence rate ratios. There will be no other changes in the study 
design nor will there be any changes needed to the originally planned analysis as a result of 
this interim analysis.
8. DATA COLLECTION AND DATA MANAGEMENT
8.1. Case Report Forms/Electronic Data Record
There is no data collection form designed for this study. The data to be used in this study are 
being collected in an existing electronic health care database. 

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8.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including serious adverse event forms, and adequate documentation 
of relevant correspondence (e.g., letters, meeting minutes, telephone calls reports).  The 
records should be retained by the investigator according to local regulations, or as specified 
in the Clinical Study Agreement, whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (e.g., retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. The 
investigator must obtain Pfizer's written permission before disposing of any records, even if 
retention requirements have been met.
9. ADVERSE EVENT REPORTING AND SERIOUS ADVERSE EVENT 
REPORTING
This study uses de-identified patient-level electronic health related databases (e-HRD), in 
which it is generally not possible to link (i.e. identify a potential association between) a 
particular product and medical event for any individual. Furthermore, while the identifiable 
patient criterion may be met, the identifiable reporter criterion will not. Thus, the minimum 
criteria for reporting an adverse event (i.e., identifiable patient, identifiable reporter, a 
suspect product, and event) are not available and adverse events are not reportable as 
individual AE reports.
However, this study protocol requires review of the patient medical chart and/or a narrative 
field in the dataset. If the reviewer identifies a SAE with explicit attribution to any Pfizer 
drug via patient chart and/or narrative review (and with an identifiable reporter), these SAEs 
should be reported to Pfizer or its representative for submission to regulatory authorities.
A serious adverse event (SAE) is defined as any untoward medical occurrence that at any 
dose:

results in death;

is life-threatening (i.e., at immediate risk of death due to the event);

requires inpatient hospitalization or prolongation of existing hospitalization;

results in persistent or significant disability/incapacity; or

is a congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 

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the patient or may require intervention to present one of the other outcomes listed in the 
definition above, the important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, 
or development of drug dependency or drug abuse.
If there is a written notation in the medical chart/narrative field indicating that a physician 
attributed a serious adverse event to a Pfizer drug, Pfizer or its representative will complete 
an SAE form within 24 hours and submit it to Pfizer Safety. Such information will not 
include any patient or physician identifying information such as name, address, or phone 
number.
10. POTENTIAL WEAKNESSES
Lack of hospitalization data: The Cegedim LPD collects data from GP offices. Therefore, 
complete records of events requiring hospitalization are not available in the database. Since 
no patient identifiers are available it is also not possible to link to any available national or 
regional registries to obtain additional information (e.g., vital status, diagnosis of 
malignancies). 
Data collection in routine care: The Cegedim LPD collects real life clinical practice 
information from the actual medical records of the patients. No study specific CRF will be 
used to collect supplemental information that are not entered in the medical records as part of 
the patient’s routine clinical care. Also, as a non-interventional study, this protocol does not 
mandate any study specific visits, procedures or laboratory tests.
Dependence on market uptake of the study medication: Bazedoxifene is a newly launched 
product in the participating countries. Since there is no active enrollment of patients (i.e., in 
contrast to a de novo prospective follow up study), the final sample size will be based on the 
rate of the uptake of the drug in the participating countries during the subject accrual period.
Potential for missing data: The data for this study will come from routine clinical care. No 
individual patient identifiers will be available. Therefore it is not possible to query the 
physicians providing the data for any missing information. 
Difference in indication for Bazedoxifene and Raloxifene: Bazedoxifene is indicated for 
the treatment of post-menopausal osteoporosis whereas Raloxifene is indicated for both the 
prevention and treatment of post-menopausal osteoporosis. As a result the characteristics of 
the cohort of women receiving Raloxifene may differ from the women who are receiving 
Bazedoxifene. It is possible that the Raloxifene cohort will have a higher proportion of 
healthier, younger women.

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11. ETHICS
11.1. Institutional Review Board (IRB)/Ethics Committee (EC)
It is the responsibility of Cegedim to have prospective approval of the study protocol, 
protocol amendments, from an appropriate IRB/EC as necessary in the participating 
countries.  All correspondence with the IRB/EC should be retained in the study File.  
11.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices such 
as Good Pharmacoepidemiology Practices (GPP) issued by the International Society for 
Pharmacoepidemiology (ISPE), the International Society for Pharmacoeconomics and 
Outcomes Research (ISPOR) guidances, Pharmaceutical Research and Manufacturers 
Association (PhRMA) guidelines and similar.
11.3. Subject Information and Consent
Not applicable.
12. COMMUNICATION AND PUBLICATION OF STUDY RESULTS
12.1. Communication of results by Pfizer
Pfizer fulfils its commitment to publicly disclose the results of studies through posting the 
results of this study on ClinicalStudyResults.org.  Pfizer posts the results of studies that fall 
into either of the following categories:

Studies that Pfizer registered on www.clincaltrials.gov regardless of the reason for 
registration; OR

All other studies for which the results have scientific or medical importance as 
determined by Pfizer.
Results are posted in two formats:  

The results of studies applicable under the US Food and Drug Administration 
Amendments Act of 2007 (FDAAA) and/or An Act Regarding Advertising by Drug 
Manufacturers and Disclosure of Clinical Trials (state of Maine Reporting 
Requirements) are posted on ClinicalTrials.gov in a tabular format called Basic 
Results.  

The results of all required studies (even if not previously registered to 
ClinicalTrials.gov) and any voluntarily registered studies are posted on 
ClinicalStudyResults.org in a format called a Pharmaceutical Research and 
Manufacturers of America (PhRMA) website synopsis (PWS), the format established 
by the ICH-E3 Clinical Study Report (CSR) Synopsis.

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For studies involving a Pfizer product, the timing of the posting depends on whether the 
Pfizer product is approved for marketing in any country at the time the study is completed:

For studies involving products already approved in any country and applicable under 
FDAAA and/or state of Maine, Pfizer posts results within one year of the primary 
outcome completion date (PCD).  For all other studies that do not involve a Pfizer 
product, Pfizer posts results one year from last, subject last visit (LSLV);

For studies involving products that are not yet approved in any country, Pfizer posts 
the results of already-completed studies within 30 days after US regulatory approval.  
or one year after the first ex-US regulatory approval of the product (if only submitted 
for approval ex-US);

For studies involving products whose drug development is discontinued before 
approval, Pfizer posts the results within one year after such discontinuation.
Primary Completion Date is defined as the date that the final subject was examined or 
received an intervention for the purposes of final collection of data for the primary outcome, 
whether the clinical trial concluded according to the pre-specified protocol or was 
terminated.
Pfizer posts citations only for publications that are accessible in recognized (searchable) 
publication databases. Single-centre results publications for a multi-centre study are 
generally not posted because they may not accurately reflect the results of the study.
13. REFERENCES 
1.
Grady, D., et al., Safety and adverse effects associated with raloxifene: multiple 
outcomes of raloxifene evaluation. Obstet Gynecol, 2004. 104(4): p. 837-44.
2.
Agresti, A., Categorical Data Analysis. Wiley, 2002. 2nd Edition.

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