SWEGHO - A PROSPECTIVE NON INTERVENTIONAL STUDY PROTOCOL WITH PRIMARY DATA COLLECTION - ASSESSMENT OF THE LONG TERM TREATMENT OUTCOMES OF GENOTROPIN TREATMENT IN GHD PATIENTS IN SWEDEN
Conditions: Growth Hormone Deficiency
Sponsor: Pfizer

PPD
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1. TABLE OF CONTENTS 
SWEGHO -A Prospective Non Interventional Study Protocol with Primary Data 
Collection - ................................................................................................................... 1 
ASSESSMENT OF THE LONG TERM TREATMENT OUTCOMES OF GENOTROPIN 
TREATMENT IN GHD PATIENTS IN SWEDEN (A628 SO MATRO PIN) ...................... 1 
1. TABLE OF CONTENTS ............................................................................................................. 2 
2. LIST OF ABBREVIATIONS ...................................................................................................... 4 
3. RESPONSIBLE PARTIES .......................................................................................................... 5 
3.1. Principal Investigator(s) of the Protocol ......................................................................... 5 
4. ABSTRACT ................................................................................................................................. 5 
ASSESSMENT OF THE LONG TERM TREATMENT OUTCOMES OF GENOTROPlN 
TREATMENT IN GHD PATIENTS IN SWEDEN (. .......................................................... 5 
5. AMENDMENTS AND UPDATES ............................................................................................. 7 
6. MILESTONES ............................................................................................................................. 7 
7. RATIONALE AND BACKGROUND ........................................................................................ 8 
8. RESEARCH QUESTION AND OBJECTIVES ......................................................................... 9 
9. RESEARCH METHODS .......................................................................................................... 10 
9.1. Studydesign .................................................................................................................. 10 
9 .2. Setting ............................................................................................................................ 10 
9.3. Inclusion criteria ............................................................................................................ 10 
9.4. Exclusion criteria ........................................................................................................... 11 
9.5. Study Period .................................................................................................................. 11 
9.6. Baseline Visit ..................................................................................................... ........... 11 
9.7. Follow-up Visits ............................................................................................................ 12 
9.8. Variables ........................................................................................................................ 12 
9.9. Data sources .................................................................................................................. 14 
9.10. Study size .................................................................................................................... 14 
9. 11 . Data 1nanagement ........................................................................................................ 15 
9.12. Data analysis ............................................................................................................... 15 
9.13. Analysis of safety ........................................................................................................ 16 
9.14. Quality control. .............................................................................................................. 16 
9 .15. Record Retention ......................................................................................................... 16 
9.16. Limitations of the research methods ........................................................................... 17 
10. PROTECTION OF HUMAN SUBJECTS .............................................................................. 17 
l 0 .1. Patient Information and Consent.. ............................................................................... 17 
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10.2. Patient withdrawal······················································································-·········· 17 
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) .................. 17 
10.4. Ethical Conduct of the Study ..................................................................................... .18 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS18 
11. l . Requirements ............................................................................................................... 18 
11.2. Reporting period .......................................................................................................... 19 
11.3. Causality assess1nent ................................................................................................... 19 
11.4. Definition of an Adverse Event. .................................................................................. 19 
11.5. Abnormal test findings ................................................................................................ 20 
11.6. Serious Adverse Events ............................................................................................... 21 
11. 7. Hospitalization ............................................................................................................ 21 
Scenarios necessitating reporting to Pfizer Safety within 24 hours ..................................... 22 
11.8. Medical device complaint reporting requirements ...................................................... 24 
l 1.9. Single reference safety document .............................................................................. .25 
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS ............. .25 
12.1 . Communication of issues ........................................................................................... .26 
13. REFERENCES ........................................................................................................................ 26 
14. LIST OF TABLES ................................................................................................................... 27 
15. LIST OF FIG.ORES ................................................................................................................. 27 
ANNEX l . LIST OF ST AND-ALONE DOCUMENTS .............................................................. .27 
ANNEX 2. KIMS ETIOLOGY CLASSIFICATION LIST .......................................................... 28 
ANNEX 3. LIST OF PUBLICATIONS BASED ON KIMS DATA ........................................... .30 
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2. LIST OF ABBREVIATIONS 
ABBREVIATIONS AND DEFINITION OF TERMS 
AE- Adverse event 
BT - Brain Tumor 
CM-Concomitant Medications 
CO-GHD - Childhood-Onset GH Deficiency 
CT- Computed Tomography 
eCRFs - electronic Case Report Forms 
FBS-Fasting Blood Sugar 
OH - Growth Hormone 
GHD - GH Deficiency 
IEC - Independent Ethics Committee 
IGF-1- Insulin-like Growth Factor 
IRB - Institutional Review Board 
LH - Lymphocytic Hypophysitis 
MRI- Magnetic Resonance Imaging 
N.A. - Not Applicable 
N I - Non lnterventional 
rhGH - recombinant human OH 
SAE - Serious Adverse Event 
SAP - Statistical Analysis Plan 
SH - Subarachnoid Hemorrhage 
SWEGHO - SWEdish Growth Hormone Outcomes 
TBI - Traumatic Brain injury 
QoL - Quality of Life 
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PPD
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Study design 
This study is as a prospective national, multi-center, non-interventional study open to adult 
hypopituitary patients with GHD who are treated with Genotropin as prescribed in clinical 
practice. 
This non-interventional study does not include pre-specified endpoints, but collects information 
from adult subjects prescribed Genotropin in clinical practice. 
Population 
Patients previously followed in KIMS®, new patients fulfilling the inclusion criteria and 
transition patients with confirmed childhood onset GHD will be asked to participate. All patients 
should be diagnosed with GHD according to the current medical standards, and treated with 
Genotropin prescribed in clinical practice. After having given their informed consent, the patient 
is enrolled in the study. Normal clinical practice may include routine diagnostic procedures such 
as; blood samples, CTs, MRI and other tests. The decision of what measures to perform is not 
pre-specified in the protocol but is based on the clinical experience, standards and judgment of 
the study investigator. Data from patient records, which align with the data to be collected in the 
database eCRF as specified in this protocol, will be collected and entered into the database. The 
data will be collected during the patients' routine visits to the clinic. 
Data sources 
No other data than what is collected during the normal clinical practice are to be entered into the 
database. Data from local labs and CT/MRI will be collected as available. A password-protected 
data entry and data management tool, Viedoc ® will be made available to study investigators 
through the Internet. Data will be manually entered into the database eCRF within Viedoc®. Only 
information obtained during the course of normal clinical practice is collected. 
A study patient code is generated by Viedoc ®for each study patient at the time of their 
enrollment into the study. Only the treating investigator or an authorized staff member has access 
to patient identifiable information using the study patient code. 
Study size 
This is a descriptive study without a pre-specified hypothesis and calculation of sample size is 
not applicable. Approximately 900 patients are expected to be included. 
The study is planned to continue for 5 years. 
Data analysis 
Study data are analyzed as often as required to address regulatory queries, safety reporting 
requirements and clinical questions posed by investigators. In addition the study data are 
analyzed to support study research projects initiated and run by investigators in partnership with 
Pfizer. 
Detailed methodology for summary and statistical analyses of data collected in this study will be 
documented in a Statistical Analysis Plan (SAP) for each project which will be dated, filed and 
maintained by the sponsor. 
Milestones 
Start of data collection is planned to October 2013, end of data collection October 2018. Final 
study report is planned to October 2019. 
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5. AMENDMENTS AND UPDATES 
Amendm 
Substantial or 
Protocol 
Summary of amendment(s) 
enl 
Date 
administrative 
section(s) 
number 
amendment 
changed 
I 
2013 
Admin 
All sections 
From KIMS Xtended to swegho 
OCT7 
2 
2014 
Adm in 
11.10 
Add safety language regarding reporting time for 
JUNE 30 
Overdose, misuse and extravasation 
3 
Adm in 
3.1 
Pfizer AB is changed to Pfizer Innovations AB 
2015 
4.0 
Table I. Updated definitions of variables 
APRTL 9 
9.8 Tabl I. 
4 
Adm in 
Requirements of Management and reporting of 
2015 
adverse events/adverse reactions regarding: 
II 
-Reporting period 
June 4 
-Causality assessment 
-Definitions of abnom1al lab findings 
-Definitions of hospitalizations 
5 
Editorial changes 
230CT 
2015 
throughout the 
Adm in 
protocol 
5 
Update reporting requirements for Non Serious 
Adverse Events 
Update reporting requirements Exposure during 
II 
pregnancy 
5 
9.8 Tabl I. 
Clarification of Data Sources 
6. MILESTONES 
Milestone 
Planned date 
Start of data collection 
30 October 2013 
End of data collection 
30 October 2018 
Final study report 
30 October 2019 
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Reason 
Change of alias of the study 
Safety language 
Change of sponsor's name 
Clarifying variables of data 
collection 
Safety Language 
Reporting requirements for 
Non Serious Adverse 
Events was not correct 
Update reporting 
requirements Exposure 
during pregnancy 
Missing information 

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7. RA TIO NALE AND BACKGROUND 
The first suggestions that growth hormone (GH) may play an important role in adults occurred as 
early as 1962 when Raben reported improved vigor, well-being, and ambition in a 35-year-old 
hypopituitary patient treated with extracted pituitary GH.1 It was only the introduction of 
recombinant human GH 2 in the middle of the 1980' s, which provided an opportunity for wider and 
more detailed studies of the effects of GH in adults. It became clear, that GH is not only an essential 
stimulator of postnatal growth and development but is also primarily a potent anabolic hormone that 
modulates a large variety of physiological functions e.g., energy balance, lipid and protein 
metabolism, body composition, body fluid control, bone growth and mineralization, cardiovascular 
function, and, finally mood, cognition, memory and learning as well as general well-being and 
quality of life (QoL ).3 
Given the broad range of GH actions, the widespread diversity in phenotype of patients with GH 
deficiency (GHD) is not at all surprising; furthermore, depending on the patients' age, different 
disease presentations should be expected and, indeed, this is the case. In children, the predominant 
presentation is growth retardation, whilst after completion of linear growth, adverse metabolic 
changes, increased cardiovascular risk, abnormal body composition, reduced bone mineral density 
and impaired QoL are the major features. Overall, the adverse effects of GHD in adults lead to an 
increased cardiovascular risk and have a negative impact on daily life. In adults the disease can 
persist from childhood - childhood-onset GHD (CO-GHD), or arise in adulthood, adult-onset GHD 
(AO-GHD). GHD may occur as an isolated hormonal deficit or be part of multiple pituitary hormone 
deficiency (panhypopituitarism). GHD in adults most frequently results from tumors in the 
hypothalamic- pituitary region or as a consequence of their treatment e.g., surgery or radiotherapy.3 
The safety and efficacy profile of GH and later recombinant human GH (rhGH) including 
Genotropin® has been demonstrated in clinical trials conducted worldwide. However, because of 
the limited number and characteristics of patients enrolled in randomized clinical trials and their 
relatively short duration of treatment in study protocols, there has been an increasing interest on the 
part of physicians to follow OH-treated adult patients prospectively during GH treatment in a real 
world clinical setting to better assess the long-term safety and treatment outcomes of GH therapy and 
generate infonnation that complements the short-term safety and efficacy data obtained from formal 
clinical trials performed for registrational purpose. 
KIMS® (Pfizer International Metabolic Database) a non-interventional study sponsored by Pfizer, 
was run between I 994 and 2012. It evaluated the long-term safety and treatment outcomes of adult 
patients treated with Genotropin in a real-world clinical setting. A non-interventional study is where 
the medicinal product(s) is (are) prescribed in the usual manner or in accordance with the terms of 
the marketing authorization. The assignment of the patient to a particular therapeutic strategy is not 
decided in advance by a trial protocol but falls within current practice and the prescription of the 
medicine is clearly separated from the decision to include the patient in the study. No additional 
diagnostic or monitoring procedures, outside the routine clinical practice, shall be applied to the 
patients and epidemiological methods shall be used for the analysis of collected data. 
Because KIMS® collected information from large patient cohorts followed in daily clinical practice 
settings and with no restrictions in terms of study duration or included participants, it generated 
medical information about clinical characteristics and patient management complementary to that 
generated by randomized clinical trials. As such, KIMS ®was particularly well-suited to capture 
information regarding rare adverse events and atypical treatment reactions, on the one hand, and 
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information on treatment outcomes that allowed for cost effective, individualized GH treatment. 
Numerous articles based upon data from KIMS have been published in the scientific literature and 
presented at scientific meetings, see ANNEX 3. 
Patients are treated with GH over a long time period, usually over several years and for some patients 
the treatment duration can even be life-long, especially for the patients with CO-GHD. Due to the 
long treatment period it is of great value to continue the assessment further. In order to further 
strengthen the data previously collected in KIMS®, this study is designed to further follow up long-
term Genotropin therapy treatment outcomes in a real-world clinical setting and to be able to 
compare patients who started treatment after 2012 with patients who started treatment in 1990-ies. 
The Swedish KIMS® investigators have in their previous participation in KIMS® showed very high 
standard of execution and the data excellent quality. Therefore this NIS is particularly well suited to 
be continued in Sweden. The usefulness ofNon-Interventional studies such as KIMS® can be 
exemplified by the article of Burman6 et al recently published in JCEM, where two important causes 
of excess mortality were identified in patients with hypopituitarism. Firstly, a lack of sufficient 
adrenal response to acute stress and intercurrent illness. Secondly, increased risk of a late appearance 
of de novo malignant brain tumors in patients who previously received radiotherapy. Both of these 
findings are important as they reflect preventable events in the management of pituitary disease. 
The median follow-up period in KIMS® Sweden was approximately 9 years. One of the goals of this 
study is to prolong the long-term follow up of Genotropin therapy for patients included in KIMS®. It 
is anticipated that the study will prolong the median follow-up period with 3-5 years for the Swedish 
population. Another goal is to identify secular trends in Genotropin treatment regime and 
characteristics of treatment outcomes over 3 decades of GH replacement in adult patients with GHD. 
Patients are to be enrolled, treated and followed at the discretion of the investigator (the treating 
physician), who will collect and enter patient data into electronic case report forms (eCRFs). This 
non-interventional study does not include a pre-specified hypothesis. 
8. RESEARCH QUESTION AND OBJECTIVES 
The overall purpose of this study is: 
I) To collect long term follow-up information of patients with GHD on Genotropin replacement 
therapy. The population are patients previously followed in the Swedish KIMS® cohort and 
adults with CO-GHD treated with growth hormone. The study collects information on long-
term treatment outcomes of Genotropin therapy as prescribed in clinical practice. 
2) To compare treatment outcome and clinical practice of patients included from 2013 with 
patients treated from the 1990-ies. 
In particular the following questions will be addressed: 
• 
Further assess the long-term treatment outcomes of GH treatment in patients who are 
prescribed and treated with Genotropin. 
• 
Further determine the relationships between clinical status, dosage schedule and response to 
Genotropin treatment. 
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l. Adult patients of 18 years of age and above and fulfilling one of the three alternatives a-c 
below; 
a) Newly diagnosed with GHD according to the current medical standard. 
b) Diagnosed with GHD before 2013 and previously treated with Genotropin and 
followed in KIMS®. 
c) Transition patients diagnosed with CO-GHD before 2013. 
2. Prescribed Genotropin at the time of inclusion. 
3. Evidence of a personally signed and dated informed consent document indicating that the 
patient has been infonned of all pertinent aspects of the study. 
9.4. Exclusion criteria 
Patients who participate in any concurrent clinical interventional trial where a non-authorized or 
authorized study medication is used, during their participation in the study. Concurrent studies which 
do not include any study interventional items (whether medications or devices) are allowed. 
9.5. Study Period 
Data are collected from the subject's inclusion of the study until the subject, or investigators decide 
upon subject's withdrawal from the study ends. 
9.6. Baseline Visit 
At baseline visit the background information about patient, history of birth, family and medical 
history, diagnosis, growth, puberty, OH treatment before start in the study (if applicable) and at study 
start, is collected. 
Patients previously followed in KTMS®, appropriate data available in KIMS® will be transferred 
automatically into the study database and used to contribute to Baseline Visit data. 
The primary and subsequent diagnosis as applicable should be entered according to the KIMS 
Etiology Classification List (Annex 3). 
The correct diagnosis code is one of the most important variables by which the study patients are 
grouped for statistical analysis. 
Depending on the diagnosis background information should be provided as specified be.low: 
• 
Brain tumour CBT) - collects additional information on treatment of tumour including results 
of MRI/CT; 
• 
Traumatic Brain Injury CTBI) - collects information on medical history related to TBI; 
• 
Subarachnoid Hemorrhage (SH) - collects information on medical history related to SH; 
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• 
Lymphocytic Hypophysitis (LH) - collects information on medical history and diagnosis 
details. 
9.7. Follow-up Visits 
At follow-up visit information specified in Table 1 will be collected at each follow up visit and 
entered manually in eCRFs. In the study this information is gathered on "return visits" eCR.Fs. 
For patients previously followed in KIMS®, data available in KIMS® will be transferred 
automatically into the study Database after the patients signed informed consent. 
Only infonnation from the patients' routine visits will be collected. 
9.8. Variables 
The variables to be captured are listed in Table 1. 
Table I.Variables to be captured (if available). 
Variable 
Role* 
Data source(s) 
Informed Consent (mandatory) 
Before Baseline 
Personally signed and dated 
Informed Consent Document 
BACKGROUND INFORMATION 
Baseline 
Patient record and or CRF 
-Age 
-Gender 
- Ethnic origin 
-Age at menarche 
-Menopause/ A menorre 
-Age at Menopause/Amenorrea 
-Puberty (Induced, Spontaneous) 
-Age at end of growth 
MEDICAL HISTORY 
Baseline 
Patient record and or CRF 
-Hypertension 
-Claudication 
-Coronary Heart Disease 
-Stroke 
-Arthrosis 
-Diabetes 
-Type I 
-Type II 
-Epilepsy 
-Neoplasm 
-Other Significant disease 
-Fractures 
FAMILY HISTORY 
Baseline 
Patient record and or CRF 
-Diabetes 
-Cardiovascular Disease 
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-Hip Fracture 
-Colon Polyps 
-Colon Cancer 
-Neoplasm (other) 
PITUITARY DISEASE 
Baseline 
-Date of Diagnose 
-Childhood onset 
-Brain Tumor 
-Visual Field deficit 
-Opthalmoplegia 
-Tumor treatment 
-Tumor Size 
-Tumor type 
DIAGNOSE OF GHD 
Baseline 
-Date of Diagnose of GI-ID 
-Test method 
-Date oftest 
BASELINE PREVIOUS GH 
Baseline 
TREATMENT 
-Treatment start date 
-Treatment stop date 
EXAMINA TlON 
Baseline, Follow up visit 
-Age 
-Weight 
-Height 
-Blood pressure 
-CT/MRl 
-Body Composition 
-Additional Hormone Abnormalities 
TREATMENT 
Baseline, Follow up visit 
-GH treatment 
-Concomitant Medication of special 
interest 
LABORATORY 
Baseline, Follow up visit 
-Glucose 
-HbAlc 
-IGF-1 
ADVERSE EVENT 
Follow up visit 
Patient record and or CRF 
Patient record and or CRF 
Patient record and or CRF 
Patient record 
Patient record 
Patient record 
Patient record and information 
obtained from the patient 
Detailed operational definitions will be included in the Statistical Analysis Plan. 
*For patients previously treated in KIMS® historical data will automatically inserted into the 
Database. 
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Concomitant Medication of Special Interest: 
It is recommended to collect all concomitant medication. The particular attention should be 
given to the following concomitant medication of special interest: 
1. Replacement of other pituitary hormone deficits: sex steroids, glucocorticoids, thyroxine 
and vasopressin 
2. Treatment of prolactin abnormalities 
3. Antihypertensive drugs 
4. Lipid lowering drugs 
5. Anti-diabetic drugs 
6. Antidepressant drugs 
7. Anti-epileptic drugs 
9.9. Data sources 
Data collected during the normal clinical practice is to be entered into the study database. Data from 
local labs and CT/MRI will be collected as available. Data will be manually entered or imported 
from archived patients records into the study database. 
Information collected during the treatment and follow up of study patients is entered into eCRFs 
contained within Viedoc®, a password protected data entry and data management tool. Viedoc ® 
will be made available to investigators through the Internet. 
Data previously entered for a subject in KIMS® may be made available in the study provided that a 
new Informed consent, including permission to use KIMS® data, is signed by the subject. 
A study patient code is generated by Viedoc ®for each study patient at the time of their enrollment 
into the study. Only the treating investigator or an authorized staff member has access to patient 
identifiable information using the study patient code. 
Each study investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the eCRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic I original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required. The eCRFs 
must be signed by the study investigator or by an authorized staff member to attest that the data 
contained on the eCRFs are correctly recorded. 
9.10. Study size 
This is a descriptive study without a pre-specified hypothesis and calculation of sample size is not 
applicable. Approximately 900 patients are expected to be included. 
The study is planned to continue for 5 years and each patient entering lhe study will be included for 
the whole time period if not prematurely with-drawn. Hence the total number will be in the range of 
900 patients (600 from KIMS® and 250 new adult patients and 50 from the confirmed childhood 
onset GHD population). 
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9.11. Data management 
As used in this protocol, the term "eCRF" is used to describe an electronic data record. An eCRF 
should be completed for each included patient. The completed original eCRFs are the sole property 
of Pfizer and should not be made available in any form to third parties, except for authorized 
representatives of Pfizer or appropriate regulatory authorities, without written permission from 
Pfizer. 
eCRFs should be completed as soon as possible during or after the patient's visit. The Investigator 
must verify that all data entries in the eCRFs are accurate and correct and is required to electronically 
sign off the clinical data. 
All entries, corrections and alterations are to be made by the Investigator or his/her authorized 
designee. Once clinical data of the eCRF have been submitted to the server, corrections to the data 
fields will be audit trailed, meaning that the reason for change, the name of the person who 
performed the change, together with time and date will be logged. Roles and rights of the site 
personnel responsible for entering the clinical data into the eCRF will be determined in advance. The 
appropriate investigational staff will answer queries generated in the application. This process is 
audit trailed meaning that the name of investigational staff, time, and date is logged. 
Any corrections to entries made in the eCRFs, must be dated, explained (if necessary) and signed. An 
audit trail of any corrections to original data entry is available in the system. 
9.12. Data analysis 
Data in this study are analyzed as often as required to address regulatory queries, safety reporting 
requirements and clinical questions posed by investigators. In addition the study data are analyzed to 
support research projects initiated and run by investigators in partnership with Pfizer. 
Detailed methodology for summary and statistical analyses of data collected in this study will be 
documented in a Statistical Analysis Plan (SAP) before any analysis can begin. If analyses are to be 
performed at several occasions (e.g. interim analyses), the respective SAPs will be dated, filed and 
maintained by the Sponsor and/or involved investigator(s). Results of these analyses are presented in 
scientific articles, posters and oral presentations at scientific meetings. 
If statistical analyses on data from this study are performed by investigators, independently of Pfizer, 
the SAP should be approved by Pfizer Medical and a Pfizer statistician. Analysis results are 
reviewed by Pfizer prior to their presentation and/or publication. 
Study data are analyzed as often as required to address regulatory queries, safety reporting 
requirements and clinical questions posed by investigators. In addition the study data are analyzed to 
support study research projects initiated and run by investigators in partnership with Pfizer. 
In general, data from all patients with correct entered data will be analyzed at regular intervals. 
Protocol deviations will be listed per patient, describing the nature of the deviation as well as the 
times and reasons for discontinuation. 
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9.13. Analysis of safety 
Safety outcomes of long-term Genotropin therapy are analyzed to provide information as requested. 
Frequency and incidence rates of AEs are calculated and compared to data on general populations, 
when available. Incidence and frequency rates of AEs are also compared between different 
subgroups in the study. 
9.14. Quality control 
The study will be monitored according to the monitoring plan. 
As used in this protocol, the term case report form (CRF) should be understood to refer to an 
electronic data record. 
A CRF should be completed for each included subject. The completed original CRFs are the sole 
prope.rty of Pfizer and should not be made available in any form to third parties, except for 
authorized representatives of Pfizer or appropriate regulatory authorities, without written permission 
from Pfizer. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, safety and 
laboratory data entered on the CRFs and any other data collection forms (source documents) and 
ensuring that they are accurate, authentic I original, attributable, complete, consistent, legible, timely 
(contemporaneous), enduring and available when required. The CRFs must be signed by the 
investigator or by an authorized staff member to attest that the data contained on the CRFs is true. 
Any corrections to entries made in the CRFs, source documents must be dated, initialed and 
explained (if necessary) and should not obscure the original entry." 
In most cases, the source documents are the hospital's or the physician's subject chart. In these cases 
data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents. In these cases, a 
document should be available at the investigator's site as well as at Pfizer and clearly identify those 
data that will be recorded in the CRF, and for which the CRF will stand as the source document. 
9.15. Record Retention 
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator agrees to 
keep records, including the identity of all participating subjects (sufficient information to link 
records, e.g., CRFs and hospital records), all original signed informed consent forms, copies of all 
CRFs, serious adverse event forms, source documents, and detailed records of treatment disposition, 
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 transfened 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. 
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9.16. Limitations of the research methods 
In order to ensure a comprehensive view of the disease it is important that a m~jority of the treated 
patients can be included. Hence both patients with complicated disease as well patients with a less 
complicated disease should be included. Further is it important to ensure that the data from the 
different hospitals are qualitatively at a high standard and complete. 
10. PROTECTION OF HUMAN SUBJECTS 
10.1. Patient Information and Consent 
All parties will ensure protection of patient personal data and will not include patient names on any 
sponsor forms, reports, publications, or in any other disclosures, except where required by laws. In 
case of data transfer, Pfizer will maintain high standards of confidentiality and protection of patient 
personal data. 
The informed consent form must be in compliance with local regulatory requirements and legal 
requirements. 
The informed consent form used in this study, and any changes made during the course of the study, 
must be prospectively approved by both the IRB/IEC and Pfizer before use. 
The investigator must ensure that each study patient, or his/her legally acceptable representative, is 
fully informed about the nature and objectives of the study and possible risks associated with 
participation. The investigator, or a person designated by the investigator, will obtain written 
informed consent from each patient or the patient's legally acceptable representative before any 
study-specific activity is performed. The investigator will retain the original of each patjent's signed 
consent form. 
10.2. Patient withdrawal 
Patients may withdraw from the study at any time at their own request, or they may be withdrawn at 
any time at the discretion of the investigator or sponsor for safety, behavioral, or administrative 
reasons. In any circumstance, every effort should be made to document patient outcome, if possible. 
The investigator should inquire about the reason for withdrawal and follow-up with the patient 
regarding any unresolved adverse events. 
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
infonnation, no further evaluations should be performed, and no additional data should be collected. 
The sponsor may retain and continue to use any data collected before such withdrawal of consent. 
10.3. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, protocol 
amendments. and informed consent fonns, and other relevant documents, (e.g., recruitment 
advertisements), if applicable, from the TRB/IEC. All correspondence with the IRB/IEC should be 
retained in the Investigator File. Copies of IRB/IEC approvals should be forwarded to Pfizer. 
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10.4. Ethical Conduct of the Study 
The study will be conducted in accordance with local legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices. 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS 
11.1. Requirements 
The table below summarizes the requirements for recording safety events on the SWEGHO 
e-CRF and for reporting safety events on the non-interventional study (NIS) adverse event 
monitoring (AEM) Report Form to Pfizer Safety. These requirements are delineated for three types 
of events: (1) serious adverse events (SAEs); (2) non-serious AEs (as applicable); and (3) scenarios 
involving drug exposure, including exposure during pregnancy, exposure during breast feeding, 
medication error, overdose, misuse, extravasation, and occupational exposure. These events are 
d fi d . h 
"D fi . . 
f 
fl 
" 
eme mt e section 
e m1t10ns o sa ety events . 
Reported on the NIS AEM 
Safety event 
Recorded on the SWEGHO 
Report Form to Pfizer 
e-CRF 
Safety within 24 hours of 
awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Scenarios involving exposure 
to a drug under study, 
including exposure during 
All (regardless of whether 
pregnancy, exposure during 
associated with an AE), 
All (regardless of whether 
breast feeding, medication 
except occupational 
associated with an AE) 
error, overdose, misuse, 
exposure 
extravasation; lack of efficacy; 
and occupational exposure. 
For each AE, the investigator must pursue and obtain information adequate both to detennine the 
outcome of the adverse event and to assess whether it meets the criteria for classification as a SAE 
(see section "Serious Adverse Events" below) 
Safety events listed in the table above must be reported to Pfizer within 24 hours of awareness of the 
event by the investigator regardless of whether the event is determined by the investigator to be 
related to a drug under study. In particular, if the SAE is fatal or life-threatening, notification to 
Pfizer must be made immediately, irrespective of the extent of available event information. This 
timeframe also applies to additional new (follow-up) information on previously forwarded safety 
event reports. In the rare situation that the investigator does not become immediately aware of the 
occurrence of a safety event, the investigator must report the event within 24 hours after learning of it 
and document the time of his/her first awareness of the events. 
For safety events that are considered serious or that are identified in the far right column of the table 
above that are reportable to Pfizer within 24 hours of awareness, the investigator is obligated to 
pursue and to provide any additional information to Pfizer in accordance with this 24-hour 
timeframe. In addition, an investigator may be requested by Pfizer to obtain specific follow-up 
information in an expedited fashion. This information is more detailed than that recorded on the 
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SWEGHO e-CRF. In general, this will include a description of the adverse event in sufficient detail 
to allow for a complete medical assessment of the case and independent detem1ination of possible 
causality. Any information relevant to the event, such as concomitant medications and illnesses must 
be provided. In the case of a patient death, a summary of available autopsy findings must be 
submitted as soon as possible to Pfizer or its designated representative. 
11.2. Reporting period 
For each patient, the safety event reporting period begins at the time of the patient's first dose of 
Genotropin® or the time of the patient's informed consent ifs/he is already exposed to Genotropin®, 
and lasts through the end of the observation period of the study, which must include at least 28 
calendar days following the last administration of a drug under study; a report must be submitted to 
Pfizer Safety (or its designated representative) for any of the types of safety events listed in the table 
above occurring during this period. If a patient was administered a drug under study on the last day 
of the observation period, then the reporting period should be extended for 28 calendar dlays 
following the end of observation. Most often, the date of informed consent is the same as the date of 
enrollment. In some situations, there may be a lag between the dates of informed consent and 
enrollment. In these instances, if a patient provides informed consertt but is never enrolled in the 
study (e.g., patient changes his/her mind about participation), the reporting period ends on the date of 
the decision to not enroll the patient. 
If the investigator becomes aware of a SAE occurring at any time after completion of the study and 
s/he considers the SAE to be related to Genotropin®, the SAE also must be reported to Pfizer Safety. 
11.3. Causality assessment 
The investigator is required to assess and record the causal relationship. For all AEs, sufficient 
information should be obtained by the investigator to determine the causality of each adverse event. 
For AEs with a causal relationship to Genotropin® follow-up by the investigator is required until the 
event and/or its sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer 
concurs with that assessment. 
An investigator's causality assessment is the determination of whether there exists a reasonable 
possibility that Genotropin® caused or contributed to an adverse event. If the investigator's final 
determination of causality is "unknown" and s/he cannot determine whether Genotropin® caused the 
event, the safety event must be reported within 24 hours. 
If the investigator cannot determine the etiology of the event buts/he detennines that Genotropin® 
did not cause the event, this should be clearly documented on the SWEGHO 
e-CRF and the NIS AEM Report Fonu. 
11.4. Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient administered a medicinal product. The event 
need not necessarily have a causal relationship with the product treatment or usage. Examples of 
adverse events include but are not limited to: 
• 
Abnormal test findings; (see below for circumstances in which an abnormal test finding 
constitutes an adverse event); 
• 
Clinically significant symptoms and signs; 
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• 
Changes in physical examination findings; 
• 
Hypersensitivity; 
• 
Progression/worsening of underlying disease; 
• 
Lack of efficacy; 
• 
Drug abuse; 
• 
Drug dependency. 
Additionally, for medicinal products, they may include the signs or symptoms resulting from: 
• Drug overdose; 
• Drug withdrawal; 
• Drug misuse; 
• Off-label use; 
• Drug interactions; 
• Extravasation; 
• Exposure during pregnancy; 
• Exposure during breast feeding; 
• Medication error; 
• Occupational exposure . 
11.5. Abnormal test findings 
The criteria for determining whether an abnormal objective test finding should be reported as an 
adverse event are as follows: 
• 
Test result is associated with accompanying symptoms, and/or 
• 
Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
• 
Test result leads to a change in study dosing or discontinuation from the study) significant 
additional concomitant drug treatment, or other therapy, and/or 
• 
Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute 
an adverse event. Any abnormal test result that is determined to be an error does not require reporting 
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10.4. Ethical Conduct of the Study 
The study will be conducted in accordance with local legal and regulatory requirements, as well as 
with scientific purpose, value and rigor and follow generally accepted research practices. 
11. MANAGEMENT AND REPORTING OF ADVERSE EVENTS/ADVERSE REACTIONS 
11.1. Requirements 
The table below summarizes the requirements for recording safety events on the SWEGHO 
e-CRF and for reporting safety events on the non-interventional study (NIS) adverse event 
monitoring (AEM) Report Form to Pfizer Safety. These requirements are delineated for three types 
of events: (1) serious adverse events (SAEs); (2) non-serious AEs (as applicable); and (3) scenarios 
involving drug exposure, including exposure during pregnancy, exposure during breast feeding, 
medication error, overdose, misuse, extravasation, and occupational exposure. These events are 
defined in the section "Definitions of safety events". 
Reported on the NlS AEM 
Safety event 
Recorded on the SWEGHO 
Re1>ort Form to Pfizer 
e-CRF 
Safety within 24 hours of 
awareness 
SAE 
All 
All 
Non-serious AE 
All 
None 
Scenarios involving exposure 
to a drug under study, 
including exposure during 
All (regardless of whether 
pregnancy, exposure during 
associated with an AE), 
AH (regardless of whether 
breast feeding, medication 
except occupational 
associated with an AE) 
error, overdose, misuse, 
exposure 
extravasation; lack of efficacy; 
and occupational exposure. 
For each AE, the investigator must pursue and obtain information adequate both to determine the 
outcome of the adverse event and to assess whether it meets the criteria for classification as a SAE 
(see section "Serious Adverse Events" below) 
Safety events listed in the table above must be reported to Pfizer within 24 hours of awareness of the 
event by the investigator regardless of whether the event is determined by the investigator to be 
related to a drug under study. In particular, if the SAE is fatal or life-threatening, notification to 
Pfizer must be made immediately, irrespective of the extent of available event information. This 
timeframe also applies to additional new (follow-up) information on previously forwarded safety 
event reports. In the rare situation that the investigator does not become immediately aware of the 
occurrence of a safety event, the investigator must report the event within 24 hours after learning of it 
and document the time of his/her first awareness of the events. 
For safety events that are considered serious or that are identified in the far right column of the table 
above that are reportable to Pfizer within 24 hours of awareness, the investigator is obligated to 
pursue and to provide any additional information to Pfizer in accordance with this 24-hour 
timeframe. In addition, an investigator may be requested by Pfizer to obtain specific follow-up 
information in an expedited fashion. This information is more detailed than that recorded on the 
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SWEGHO e-CRF. Jn general, this will include a description of the adverse event in sufficient detail 
to allow for a complete medical assessment of the case and independent determination of possible 
causality. Any information relevant to the event, such as concomitant medications and illnesses must 
be provided. In the case of a patient death, a summary of available autopsy findings must be 
submitted as soon as possible to Pfizer or its designated representative. 
11.2. Reporting period 
For each patient, the safety event reporting period begins at the time of the patient's first dose of 
Genotropin® or the time of the patient's informed consent ifs/he is already exposed to Genotropin®, 
and lasts through the end of the observation period of the study, which must include at least 28 
calendar days following the last administration of a drug under study; a report must be submitted to 
Pfizer Safety (or its designated representative) for any of the types of safety events listed in the table 
above occurring during this period. If a patient was administered a drug under study on the last day 
of the observation period, then the reporting period should be extended for 28 calendar days 
following the end of observation. Most often, the date of informed consent is the same as the date of 
enrollment. In some situations, there may be a lag between the dates of informed consent and 
enrollment. In these instances, if a patient provides informed consent but is never enrolled in the 
study (e.g., patient changes his/her mind about participation), the reporting period ends on the date of 
the decision to not enroll the patient. 
If the investigator becomes aware of a SAE occurring at any time after completion of the study and 
s/he considers the SAE to be related to Genotropin®, the SAE also must be reported to Pfizer Safety. 
11.3. Causality assessment 
The investigator is required to assess and record the causal relationship. For all AEs, sufficient 
information should be obtained by the investigator to determine the causality of each adverse event. 
For AEs with a causal relationship to Genotropin® follow-up by the investigator is required until the 
event and/or its sequelae resolve or stabilize at a level acceptable to the investigator, and Pfizer 
concurs with that assessment. 
An investigator's causality assessment is the determination of whether there exists a reasonable 
possibility that Genotropin® caused or contributed to an adverse event. If the investigator's final 
determination of causality is "unknown" ands/he cannot determine whether Genotropin® caused the 
event, the safety event must be reported within 24 hours. 
If the investigator cannot determine the etiology of the event but s/he determines that Genotropin® 
did not cause the event, this should be clearly documented on the SWEGHO 
e-CRF and the NIS AEM Report Form. 
11.4. Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient administered a medicinal product. The event 
need not necessarily have a causal relationship with the product treatment or usage. Examples of 
adverse events include but are not limited to: 
• 
Abnormal test findings; (see below for circumstances in which an abnormal test finding 
constitutes an adverse event); 
• 
Clinically significant symptoms and signs; 
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• 
Changes in physical examination findings; 
• 
Hypersensitivity; 
• 
Progression/worsening of underlying disease; 
• 
Lack of efficacy; 
• 
Drug abuse; 
• 
Drug dependency. 
Additionally, for medicinal products, they may include the signs or symptoms resulting from: 
• 
Drug overdose; 
• 
Drug withdrawal; 
• 
Drug misuse; 
• 
Off-label use; 
• 
Drug interactions; 
• 
Extravasation; 
• 
Exposure during pregnancy; 
• 
Exposure during breast feeding; 
• 
Medication error; 
• 
Occupational exposure. 
11.5. Abnormal test findings 
The criteria for determining whether an abnonnal objective test finding should be reported as an 
adverse event are as follows: 
• 
Test result is associated with accompanying symptoms, and/or 
• 
Test result requires additional diagnostic testing or medical/surgical intervention, and/or 
• 
Test result leads to a change in study dosing or discontinuation from the study, significant 
additional concomitant drug treatment, or other therapy, and/or 
• 
Test result is considered to be an adverse event by the investigator or sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not constitute 
an adverse event. Any abnormal test result that is determined to be an error does not require reporting 
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as an adverse event. 
11.6. Serious Adverse Events 
A serious adverse event is any untoward medical occurrence in a patient administered a medicinal or 
nutritional product (including pediatric formulas) at any dose that: 
• 
Results in death; 
• 
Is life-threatening; 
• 
Requires inpatient hospitalization or prolongation of hospitalization (see below for 
circumstances that do not constitute adverse events); 
• 
Results in persistent or significant disability/incapacity (substantial disruption of the ability to 
conduct normal life functions); 
• 
Results in congenital anomaly/birth defect. 
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event. An important medical event may not be immediately life-threatening and/or result in 
death or hospitalization. However, if it is determined that the event may jeopardize the patient or 
may require intervention to prevent one of the other outcomes listed in the definition above, the 
important medical event should be reported as serious. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; or development 
of drug dependency or drug abuse. 
Additionally, any suspected transmission via a Pfizer product of an infectious agent, pathogenic or 
non-pathogenic, is considered serious. The event may be suspected from clinical symptoms or 
laboratory findings indicating an infection in a patient exposed to a Pfizer product. The terms 
"suspected transmission" and "transmission" is considered synonymous. These cases are considered 
unexpected and handled as serious expedited cases by PV personnel. Such cases are also considered 
for reporting as product defects, if appropriate. 
11. 7. Hospitalization 
Hospitalization is defined as any initial admission (even if Jess than 24 hours) to a hospital or 
equivalent healthcare facility or any prolongation to an existing admission. Admission also includes 
transfer within the hospital to an acute/intensive care unit (e.g., from the psychiatric wing to a 
medical floor, medical floor to a coronary care unit, neurological floor to a tuberculosis unit). An 
emergency room visit does not necessarily constitute a hospitalization; however, an event leading to 
an emergency room visit should be assessed for medical importance. 
Hospitalization in the absence of a medical AE is not in itself an AE and is not reportable. For 
example, the following reports of hospitalization without a medical AE are not to be reported. 
• 
Social admission (e.g., patient has no place to sleep) 
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• 
Administrative admission (e.g., for yearly exam) 
• Optional admission not associated with a precipitating medical AE (e.g.~ for elective cosmetic 
surgery) 
• 
Hospitalization for observation without a medical AE 
• 
Admission for treatment of a pre-existing condition not associated with the development of a new 
AE or with a worsening of the pre-existing condition (e.g., for work-up of persistent pre-
treatment lab abnormality) 
• 
Protocol-specified admission during clinical study (e.g., for a procedure required by the study 
protocol) 
Scenarios necessitating reporting to Pfizer Safety within 24 hours 
Scenarios involving exposure during pregnancy, exposure during breastfeeding, medication error, 
overdose, misuse, extravasation, lack of efficacy, and occupational exposure are described below. 
Exposure during pregnancy 
An exposure during pregnancy (EDP) occurs if: 
I. A female becomes, or is found to be, pregnant either while receiving or having been exposed 
to (e.g., environmental) Genotropin® or the female becomes, or is found to be, pregnant after 
discontinuing and/or being exposed to Genotropin® (maternal exposure). 
An example of environmental exposure would be a case involving direct contact with a Pfizer 
product in a pregnant woman (e.g., a nurse reports that she is pregnant and has been exposed 
to chemotherapeutic products). 
2. A male has been exposed, either due to treatment or environmental exposure to Genotropin® 
prior to or around the time of conception and/or is exposed during the partner pregnancy 
(paternal exposure). 
As a general rule, prospective and retrospective exposure during pregnancy reports from any source 
is reportable irrespective of the presence of an associated AE and the procedures for SAE reporting 
should be followed. 
If a study participant or study participant's partner becomes, or is found to be, pregnant during the 
study participant's treatment with Genotropin®, this information must be submitted to Pfizer, 
irrespective of whether an adverse event bas occurred using the NJS AEM Report Form and the EDP 
Supplemental Form. 
In addition, the infonnation regarding environmental exposure to Genotropin® in a pregnant woman 
(e.g., a subject reports that she is pregnant and has been exposed to a cytotoxic product by inhalation 
or spillage) must be submitted using the NIS AEM Report Form and the EDP supplemental form. 
This must be done irrespective of whether an AE has occurred. 
Information submitted should include the anticipated date of delivery (see below for information 
related to termination of pregnancy). 
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Follow-up is conducted to obtain general information on the pregnancy; in addition, follow-up is 
conducted to obtain information on EDP outcome for all EDP reports with pregnancy outcome 
unknown. A pregnancy is followed until completion or until pregnancy termination (e.g., induced 
abortion) and Pfizer is notified of the outcome. This information is provided as a follow up to the 
initial EDP report. In the case of a live birth, the structural integrity of the neonate can be assessed at 
the time of birth. In the event of a termination, the reason(s) for termination should be specified and, 
if clinically possible, the structural integrity of the terminated fetus should be assessed by gross 
visual inspection (unless pre-procedure test findings are conclusive for a congenital anomaly and the 
findings are reported). 
If the outcome of the pregnancy meets the criteria for an SAE (e.g., ectopic pregnancy, spontaneous 
abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a live born, a terminated 
fetus, an intrauterine fetal demise, or a neonatal death]), the procedures for reporting SA Es should be 
followed. 
Additional information about pregnancy outcomes that are reported as SAEs follows: 
• 
Spontaneous abortion includes miscaniage and missed abortion; 
• 
Neonatal deaths that occur within 1 month of birth should be reported, without regard to 
causality, as SAEs. In addition, infant deaths after 1 month should be reported as SAEs when 
the investigator assesses the infant death as related or possibly related to exposure to 
investigational product. 
Additional infom1ation regarding the exposure during pregnancy may be requested. Further follow-
up of birth outcomes will be handled on a case-by-case basis (e.g., follow-up on preterm infants to 
identify developmental delays). 
In the case of paternal exposure, the study participant will be provided with the Pregnant Partner 
Release of Information Form to deliver to his partner. It must be documented that the study 
participant was given this letter to provide to his partner. 
Exposure during breastfeeding 
Scenarios of exposure during breastfeeding must be reported, inespective of the presence of an 
associated AE. An exposure during breastfeeding report is not created when a Pfizer drug 
specifically approved for use in breastfeeding women (e.g., vitamins) is administered in accord with 
authorized use. However, if the infant experiences an AE associated with such a drug's 
administration, the AE is reported together with the exposure during breastfeeding. 
Medication error 
A medication error is any unintentional enor in the prescribing, dispensing or administration of a 
medicinal product that may cause or lead to inappropriate medication use or patient harm while in the 
control of the health care professional, patient, or consumer. Such events may be related to 
professional practice, health care products, procedures, and systems including: prescribing; order 
communication; product labeling, packaging, and nomenclature; compounding; dispensing; 
distribution; administration; education; monitoring; and use. 
Medication errors include: 
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• 
Near misses, involving or not involving a patient directly (e.g., inadvertent/erroneous 
administration, which is the accidental use of a product outside of labeling or prescription on 
the part of the healthcare provider or the patient/consumer); 
• 
Confusion with regard to invented name (e.g., trade name, brand name). 
The investigator must submit the following medication errors to Pfizer irrespective of the presence of 
an associated AE/SAE: 
• 
Medication errors involving patient exposure to the product, whether or not the medication 
error is accompanied by an AE. 
• 
Medication errors that do not involve a patient directly (e.g., potential medication errors or 
near misses). When a medication error does not involve patient exposure to the product the 
following minimum criteria constitute a medication error report: 
• 
An identifiable reporter; 
• 
A suspect product; 
• 
The event medication error. 
Overdose, Misuse, Extravasation 
Reports of overdose, misuse, and extravasation associated with the use of a Pfizer product are 
reported to Pfizer by the investigator, irrespective of the presence of an associated AE/SAE. 
Lack of Efficacy 
Reports of lack of efficacy to a Pfizer product are reported to Pfizer by the investigator, irrespective 
of the presence of an associated AE/SAE or the indication for use of the Pfizer product. 
Occupational Exposure 
Reports of occupational exposure to a Pfizer product are reported to Pfizer by the investigator, 
irrespective of the presence of an associated AE/SAE. 
11.8. Medical device complaint reporting requirements 
All complaints about medical devices, regardless of whether the medical device complaint is 
associated with an AE, will be collected on the applicable pages within the eCRF. This includes 
potential near incident or malfunctions associated with the use of a medical device product. An 
incident or malfunction is an event that might have led to death or serious deterioration in health, or 
if it occurred again, might have led to death or serious deterioration in health. 
Pfizer is to be notified of all medical device complaints within 24 hours of awareness of the event by 
the investigator. 
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Swedish Procedure for a Medical device complaint that is not associated with an AE: 
The following information is needed for filing a claim file: 
• 
An identifiable Pfizer product. If possible, with device number and batch number. 
• 
A description of a fault with the device. 
• 
Complaints sample may need to be requested for examination. 
The complaint should be sent to: 
E-mail address for device complaints: MC-Sweden.Reklamationer@pfizer.com 
Address for sending samples of device: Pfizer AB, Reklamationer, Vetenskapsvagen 12, 191 90 
Sollentuna, Sweden 
Tel. 08-5505 2000, ask for complaint manager. 
11.9. Single reference safety document 
The SmPC for Genotropin as registered in Sweden is the reference safety document for this study 
and should be used by the investigator for prescribing purposes and guidance. 
12. PLANS FOR DISSEMINATING AND COMMUNICATING STUDY RESULTS 
This NJ Study will be registered by Pfizer on www.clincaltrials.gov. 
All efforts will be made to ensure that the trial protocol and results arising from the trial are 
published in an established peer-reviewed journal. 
The following types of data output will be available: 
I. "Questions to the study database" posed by Investigators and relating to the clinical issues on 
hypopituitarism and its treatment. The answers to these requests are for the personal use of 
Investigators in their clinical practice. They must not be publically presented or published. 
2. Publications and/ or scientific presentations which communicate the results of data analyses. 
Publications based on the national data are discussed and 
endorsed by the advisory board. 
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Pfizer has no objection to an Investigator publishing his/her part of the study, or to reporting 
their data after agreement between participating sites. In all cases, communications are 
compliant with Pfizer publication policies and other Standard 
Operating Procedures, as required. 
Investigators are entitled to propose a research project to be performed on the study data. Such 
proposals should be endorsed by the Advisory Board in partnership with Pfizer. 
Pfizer has no objection to publication by Investigator of any information collected or generated by 
Investigator, whether or not the results are favorable to the Investigational Drug. However, to ensure 
against inadvertent disclosure of Confidential Infomrntion or unprotected Inventions, Investigator 
will provide Pfizer an opportunity to review any proposed publication or other type of disclosure 
before it is submitted or otherwise disclosed. 
Investigator will provide manuscripts, abstracts, or the full text of any other intended disclosure 
(poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer at least 30 days 
before they are submitted for publication or otherwise disclosed. If any patent action is required to 
protect intellectual property rights, Investigator agrees to delay the disclosure for a period not to 
exceed an additional 60 days. 
Investigator will, on request, remove any previously undisclosed Confidential Information (other 
than the Study results themselves) before disclosure. 
If the Study is part of a multi-center study, Investigator agrees that the first publication is to be a joint 
publication covering all centers. However, if a joint manuscript has not been submitted for 
publication within 12 months of completion or termination of the Study at all participating sites, 
Investigator is free to publish separately, subject to the other requirements of this Section. 
12.J. Communication of issues 
In the event of any prohibition or restriction imposed (e.g., clinical hold) by an applicable Competent 
Authority in any area of the world, or if the investigator is aware of any new information which 
might influence the evaluation of the benefits and risks of Genotropin, Pfizer should be informed 
immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures taken by 
the investigator to protect the study patients against any immediate hazard, and of any serious 
breaches of this NI study protocol that the investigator becomes aware of. 
13.REFERENCES 
1. Raben AS. Clinical use of human growth hormone. New England Journal oflvfedicine 1962 
266 82-86. 
2. Olson KC, Fenno J, Lin N, Harkins RN, Snider C, Kohr WH, Ross MJ, Fodge D, Prender G, 
Stebbing N. 1981 Purified human growth hormone from E.coli is biologically active. Nature 
1981 293 :408-11. 
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3. Carroll PV & Christ ER and the members of Gro\.\1h Hormone Research Society Scientific 
Committee: Bengtsson B-A, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, 
Laron Z, Sizonenko P, Sank.sen PH, Tanaka T & Thorner M. Growth hormone deficiency in 
adulthood and the effects of growth hormone replacement: a review. J Clin Endocrinol Metab 
1998 83 382-395. 
4. Ho K.Y. on behalf of the 2007 GH Deficiency Consensus Workshop Participants, Consensus 
Guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the 
GH Research Society in association with the European Society for Pediatrics Endocrinology, 
Japan Endocrine Society, and Endocrine Society of Australia Eur J Endocrinol 2007 
157 695-700. 
5. Clayton PE, Cuneo RC, Juul A, Monson JP, Shalet SM, Tauber M Consensus statement on 
the management of the GI-I-treated. European Journal ofEndocrinology(2005) 152 165-170 
6. Burman P, Mattsson AF, Johannsson G, Hoybye C, Holmer H, Dahlqvist P, Berinder K, 
Engstrom BE, Ekman B, Erfurth EM, Svensson J, Wahlberg J, Karlsson FA. Deaths Among 
Adult Patients with Hypopituitarism: Hypocortisolism During Acute Stress, and De Novo 
Malignant Brain Tumors Contribute to an Increased Mortality. - a KIMS database analysis. J 
Clin Endocrinol Metab 2013 Mar 1 
14. LIST OF TABLES 
Table J.Variables to be captured in SWEGHO. 
15. LIST OF FIGURES 
None 
ANNEX 1. LIST OF STAND-ALONE DOCUMENTS 
None 
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ANNEX 2. KJMS ETIOLOGY CLASSIFICATION LIST 
Idiopathic 
I. I 
Idiopathic OHO 
Congenital 
Genetic cause ofGHD 
2.1.1.1 
2. 1.1.2 
2. 1. 1.3 
2. 1.1.9 
OH-gene-defect (Type I A dominant or recessive) 
Gil gene-defect (specify) 
2.1.2. 1 
2. 1.2.2 
2. 1.2.3 
2.1.2.4 
2.1.2.S 
2. 1.2.6 
2. 1.2.9 
2.1.3. l 
2.1.3.2 
2.1.3.3 
2.1.3.9 
2.1.4.1 
2.1.4.9 
2.1.S. I 
2.1.S.9 
2. 1.6. 1 
2. 1.6.2 
2.1.6.3 
2.1.6.9 
2.1.9 
GHRH gene-defect (specify) 
Other genetic cause of GHD (specify) 
Central malformation 
Septo-optic dysplasia 
Empty sella syndrome (including pituitary aplasia) 
Solitary central maxillary incisor syndrome 
Mid-line palatal cleft 
Arachnoid cyst 
Congenital hydrocephalus 
Other central malformation (specify) 
Complex syndrome with congenital GHD 
Fanconi pancytopenia 
Rieger syndrome 
EEC syndrome (Ectrodactyly-Ectodermal Dysplasia-Clcfting syndrome) 
Other complex syndrome with congenital GHD (specify) 
Prenatal infection 
Rubella 
Other than rubella prenatal infection (specify) 
Bio-inactive OH syndrome 
Kowarski type 
Other than Kowarski type bio-inactive UH syndrome (specify) 
Functional GI-ID 
OH-receptor defect (Laron Type) 
GI 1-receptor/postreeeptor defect (specify) 
IGF resistance (specify) 
Other functional GI-ID (specify) 
Congenital unknown 
Acquired 
Tumors of the pituitary/hypothalamic area 
Craniopharyngioma 
2.2.1.1 
2.2.1 .2 
2.2.1.3 
Germ cell tumours (specify: dysgerminoma. pincaloma) 
Hamartoma 
Adenoma 
2.2.1 .4.1 Non-secreting (non-functioning pituitary adcnoma - NfPA) 
2.2.1.4.2 ACTH (Cushing disease) 
2.2.1.4.3 GH (acromegaly) 
2.2.1.4.4 Prolactin (prolactinoma) 
2.2.1.4.S Gonadotropin 
2.2.1.4.6 TSH 
2.2.1.4.7 Co-secreting (specify) 
2.2.1.4.9 Other adenoma (specify) 
2.2. 1.5 
Cyst (specify; Rathke's. epi.dermoid, dermoid) 
2.2.1.6 
Glioma 
2.2.1.7 
Meningioma 
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Schwannoma 
Chordoma 
Primary pituitary carcinoma 
Sarcoma 
Metastatic carcinoma 
Hematologic metastases 
2.2.1.8 
2.2. 1.1 0 
2.2.1.1 1 
2.2.1.12 
2.2.1.13 
2.2.1.14 
2.2.1.9 
Other tumors of pituitary/hypothalamic (specify) 
Cranial tumors distant from the pituitary/hypothalamic area 
Astrocytoma 
Ependymoma 
Glioma 
Medulloblastoma 
Nasopharyngeal tumour 
2.2.2.1 
2.2.2.2 
2.2.2.3 
2.2.2.4 
2.2.2.5 
2.2.2.9 
Other cranial tumors distant from the pituitary/hypothalamic area (specif)') 
Treatment for malignancy outside the cranium 
Leukemia 
2.2.3.1.1 Lymphatic leukemia 
2.2.3.1.2 Myeloid leukemia 
2.2.3.1.3 Aplastic leukemia 
2.2.3.1. 9 Other leukemia (specify) 
Lymphoma 
2.2.3.2.1 Hodgkin lymphoma 
2.2.3.2.2 Non-Hodgkin lymphoma 
2.2.3.2.9 Other lymphoma (specify) 
Solid tumor 
2.2.3.3 
Solid tumor (specify) 
Other causes of acquired GHD 
Head trauma/ injury 
2.2.4.1 .1 Perinatal head trauma 
2.2.4.1.2 Traumatic brain injury 
2.2.4.2 
CNS infection (specify; meningitis, encephalitis, septic cavernous sinus) 
2.2.4.3 
Hydrocephalus 
2.2.4.4 
Granulomatous diseases (specify: sarcoidosis. tuberculosis, syphilis, fungal) 
2.2.4.5 
Langerhans cell histiocytosis (histiocytosis X, eosinophilic granuloma 1-land-Schilller-Christian disease) 
Vascular system 
2.2.4.6. 1 Infarction (apoplexy) 
2.2.4.6.2 Postpartum necrosis (Sheehan syndrome) 
2.2.4.6.4 Aneurysm 
2.2.4.6.5 Sickle cell anemia 
2.2.4.6.6 Thalassaemia 
2.2.4.6 7 Subarachnoid hemorrhage 
2.2.4.6.9 Other vascular (specify) 
2.2.4.7 
Lymphocytic hypophysitis 
2.2.4.8 
Hemochromatosis 
2.2.4.9 
Other (specify) 
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ANNEX 3. LIST OF PUBLICATIONS BASED ON KIMS DAT A 
KIMS Reference List - full articles only 
Articles (#peer-reviewed} 
1998 
I. 
( I )Wilster Chr et al Verminderte lnzidenz von Nebenwirkungen einer Wachsturshormontherapie bei 404 Patienten 
mit Hypophyseninsuffizienz-Ergebnisse einer multicenter-Anwendungsbeobachtung. Medizinische Klinik 1998; 
93( 10): 585-91. Original paper. 
1999 
2000 
2001 
2. 
Ranke M., Dowie J., KIGS and KlMS as Tools for Evidence-Based Medicine Honn Res 1999; 51 (suppl l ): 
83-86 Review 
3. 
(2)Abs, R et al. GH Replacement in 1034 growth hormone deficient hypopituitary adults: demographic and 
clinical characteristics, dosing and safety. Clinical Endocrinology (1999) 50, 703-713. Original paper 
4. 
(3)Bengtsson, B-A et al. The effects of treatment and the individual responsiveness to GH replacement therapy 
in 665 OH-deficient adults. JCEM l 999;84:3929-35. Original paper 
5. 
Bengtsson, B-A et al. Growth hormone replacement therapy is not associated with any increase in mortality. 
JCEM 1999;84:4291-2. Lefler to the editor 
6. 
(4) Monson J P et al Growth Honnone Deficiency and Replacement in Elderly Hypopituitary Adults. Clinical 
Endocrinology, 2000; 53:281-9. Original paper 
7. 
Monson JP et al. Can growth hormone therapy cause diabetes? Lancet 2000;355: 1728. letter to the editor 
8. 
Cowell CT., Wilster Chr The Effects of Growth Hormone Deficiency and Growth Hormone Replacement 
Therapy on Bone Horm Res 2000; 54 (suppl I): 69-74 Review 
9. 
Wuster C., Fracture Rates in Patients with Growth Hormone Deficiency Horm Res 2000; 54 (suppl 1 ): 31-35 
Review 
10. (5)Wilster Chr et al. The Influence of Growth Hormone Deficiency, Growth Hormone Replacement Therapy, 
and Other Aspects ofHypopituitarism on Fracture Rate and Bone Mineral Density. J Bone Mineral Res 2001; 
Vol 16, No 2:398-405. Original paper 
11. (6)Hernberg-Stahl E et al. Healthcare Consumption Decreases in Parallel with Improvements in Quality of Life 
during GH Replacement in Hypopituitary Adults with GH deficiency. JCEM 2001; Vol 86 (11):5277-5281. 
Original paper 
12. Svensson Jet al. Body Composition and Quality of Life as Markers of the Efficacy of Growth Hormone 
Replacement Therapy in Adults. Honn Res 200 l ;55 (suppl 2):55-60. Review 
13. Wilton P. Safety in Growth Hormone Replacement Therapy: A Matter of Varied Responsiveness? Honn Res 
2001 ;55(suppl 2):61-64. Review 
2002 
14. (?)Feldt-Rasmussen U et al Growth hormone deficiency and replacement in hypopituitary patients previously 
treated for acromegaly and Cushing's European Journal of Endocrinology (2002) 146 67 - 74 . Original paper 
15. Abs R, Verhelst J. Long-Tenn Growth Hormone Replacement Therapy in .Hypopituitary Adults Drugs 2002; 
62 (16): 2399- 2412 review 
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2003 
16. 
l 7. 
18. 
l9. 
Monson JP., Jonsson P., Aspects of Growth Hormone (GH) Replacement in Elderly Patients with GI-I 
Deficiency: Data from KIMS Horm Res 2003;55 (suppl 1):1 12-120. original paper 
(8)Simon Dixon (MSc), Phil McEwan (PhD), Craig J. Currie (PhD); on behalf of the KIMS International 
Board; Indirect estimation of the health utility of treatment in adults with growth hormone deficiency; Journal 
of Outcomes Research; 2003 vol. 7: 1-12 Original paper 
Abs R. Update on the diagnosis ofGH deficiency in adults; European Journal of Endocrinology, Supplement. 
Vol 148(2) (pp S3-S8), 2003. Review 
Monson JP. Long-term experience with GH replacement therapy: Efficacy and safety; European Journal of 
Endocrinology, Supplement. Vol 148(2) (pp S9-Sl4}, 2003. Review 
20. Monson JP. KIMS: Treating adult GH deficiency; The Endocrinologist, Summer 2003 (68) p. 10 Commentmy 
(9)Brabant G, Von Zur Milhlen A, Wiister C, Ranke MB, Kratzsch J, Kiess W, Ketelslegers J-M, Wilhelmsen 
L, Hutten L, Saller B, Mattsson A, Wilde J, Schemer R, Kann P. Serum Insulin-Like Growth Factor f Reference 
2004 
2005 
21. 
Values for an Automated Chemiluminescence Immunoassay System: Results from a Multicenter 
Study; Hormone Research 2003. 60:53-60 Original paper 
22. ( I O)Lisett C., Jonsson P., Monson JP. Shalet SM Determinants of IGF-1 status in a large cohort of growth-
hormone deficient (GHD) subjects: the role of timing of onset ofGHD; Clinical endocrinology (2003) 59; 
773-778 Original paper 
23. (I l)Mukhe1jee A., Monson JP., Jonsson PJ., Trainer PJ., Shalet S., Seeking the optimal target range for insulin-
like growth factor I during the treatment of adult growth hormone disorders; JCEM 2003 88 (12}; 5865-5870 
Original paper 
24. (12)Svensson J., et al. Three-Years of Growth Hormone (GH) Replacement Therapy in GH-Deficient Adults: 
Effects on Quality of Life, Patient-Reported Outcomes and Healthcare Consumption GH and IGF-1 Research 
2004Jun; 14(3):207-15. Original paper 
25. ( I 3)Hugo L. Fideleff, et.al Adult growth hormone deficiency metabolic alternations and evaluation of different 
risk groups; Medicina (Buenes Aires) 2004; 64: 13-19 Original paper 
26. ( I 4)Geffner M., Lundberg M., Koltowska - Haggstrom M., Abs R., Verhelst J., Erfurth, Pat Kendall-Taylor E-
M., Price DA., Jonsson P., Bakker B., Changes in height, weight, and BMI in children with craniopharyngioma 
after three years of growth hormone therapy: analysis of KIGS (Pfizer International Growth Database) Journal 
of Clinical Endocrinology and Metabolism 2004; 89 ( 11 ): 5435-5440 Original paper 
27. (15)Kendall-Taylor P., JOnsson PJ., Abs R., Erfurth EM., Koltowska - Haggstrom M., Price DA., Verhelst J. 
The Clinical, Metabolic, Endocrine Features and Quality of Life in Adults with Childhood-Onset 
Craniopharyngioma Compared with Adult-Onset Craniopharyngioma. European Journal of Endocrinology 
2005 152 557- 567 Original paper 
28. (16)Casanueva FF., Leal Cerro A., Koltowska-Haggstrom M., Jonsson P., G6th Ml. Traumatic Brain Injury as 
a Relevant Cause of Growth Hormone Deficiency in Adults. A KIMS Based Study. Archives of Physical 
Medicine and Rehabilitation March Vol 86; No.3;463-468 Original paper 
29. (17)Kele~timur F., Jonsson P., Molvalilar S., Gomez JM., Auemhammer CJ., Colak R., Koltowska -
Haggstrom M., Goth Ml., Sheehan's syndrome: baseline characteristics and effects of2 years of growth 
hormone replacement therapy in 9 1 patients in KIMS - Pfizer International Metabolic Database. European 
Journal of Endocrinology 2005 152 581- 587 Original paper 
30. ( I 8)Verhelst J., et al. Baseline characteristics and response to 2 years of growth hormone replacement of 
hypopituitary patients with growth hormone deficiency due to adult-onset craniopharyngioma in comparison to 
patients with non-functioning pituitary adenoma: data from Kl MS (Pfizer International Metabolic Database) 
Journal of Clinical Endocrinology & Metabolism 2005 90(8): 4636-46430riginal paper 
31. ( 19)Koltowska-Haggstrom M., et al. Quality of Life Assessment of Growth Hormone Deficiency in Adults 
(QoL-AGHDA): comparison of normative reference data for the general population of England and Wales with 
results for adult hypopituitary patients with growth hormone deficiency, Hormone Research, 2005 64:46-54 
Original paper 
32. (20)Abs R., Mattsson AF., Bengtsson B-A., Feldt-Rasmussen U., Goth Ml., Koltowska-Haggstrom M., 
Monson JP., Verhelst J .• Wilton P. Isolated growth hormone (GH) deficiency in adult patients: baseline clinical 
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2007 
characteristics and responses to GI-I replacement in comparison with hypopituitary patients. A sub-analysis of 
the Kl MS database. Growth Horn1one & IGF Research 2005 2005 15(5): 349-359 Original paper 
33. (21)Mah PM., Webster J., Jt>nsson P., Feldt-Rasmussen U., Koltowska-Haggstrom M., Ross RJM., Oestrogen 
replacement in hypopituitary women offe1tile years Journal of Clinical Endocrinology & Metabolism 90 (11) 
5964-5969 2005 doi: 10.12 IO(jc.2005-1207 Original paper used for IP (as of 5 October 2006) articles 
published until 2005 (papers 2006 were not included) 
34. (22)Saller B., Mattsson AF., Kann PH., Koppeschaar HP., Svensson J., Pompen M., Koltowska-Haggstrt>rn M. 
Healthcare utilization, quality of life and patient-reported outcomes during two years of growth hormone (GI-I) 
replacement therapy in GI-I-deficient adults - comparison between Sweden, The Netherlands and Germany; . 
European Journal of Endocrinology 2006 154 843-850 Original paper 
35. (23)Koltowska-Haggstrom M., Mattsson AF., Monson JP., Kind P., Badia X., Casanueva FF., Busschbach J., 
Koppeschaar HPF., Johannsson G., Does Jong-term growth hormone replacement therapy in hypopituitary 
adults with growth-hormone deficiency normalise quality of life? European Journal of Endocrinology 2006 
155 109-1 19 Original paper 
36. (24) Abs R., Feldt-Rasmussen U., Mattsson AF., Monson JP., Bengtsson BA., Goth Ml., Wilton P., 
Koltowska-Haggstrom M. Determinants of Cardiovascular Risk in 2589 Hypopituitary Growth Hormone-
Deficient Adults - a KIMS Database Analysis - European Journal of Endocrinology 2006 155 79-90 Original 
paper 
37. (25)Maiter D., Abs R., Johannsson G., Scanlon M., JOnsson PJ., Wilton P., and Koltowska-Haggstrt>m M., 
Baseline characteristics and response to growth hormone (GH) replacement ofhypopituitary patients previously 
irradiated for pituitary adenoma or craniopharyngioma: data from KIMS (Pfizer International Metabolic 
Database) European Journal of Endocrinology 2006 155 253-260 Original paper 
38. 
39. 
40. 
41. 
42. 
(26)Filipsson H, Monson JP, Koltowska-Haggstrom M, Mattsson A, Johannsson G, The impact of 
glucocorticoid replacement regimens on metabolic outcome and comorbidity in hypopituitary patients Journal 
of Clinical Metabolism and Endocrinology 2006 91: 3954 - 3961 . 
(27) FideleffH L;Boquete H; Giaccio A;Sobrado P; KJMS Argentine Group Medium and long term outcome of 
growth hormone therapy in grov.1:h hormone deficient adults Medicina 2006,66.296-302 
(28) Brue T., Borson-Chazot F., Delemer B., Schlienger J.-L., Chauchat A., Pion I., Touraine P. KlMS 
observational study ofGH therapy in OH-deficient adults: 12 month follow-up analysis of the French cohott 
Ann. Endocrinol., 2006; 67,4: 331-337. 
(29)Kohowska-Haggstrom M., Jonsson B., Isacson D., Bingefors K., Using EQ-5D to derive general 
population-based utilities for the Quality of Life-Assessment of Growth Hormone Deficiency in Adults (QoL-
AGHDA Value in Health 2007 10 (I): 73-8/ Original paper 
(30) Svensson J, Finer N, Bouloux P, Bevan J, Jonsson B, Mattsson AF, Lundberg M, Harris PE, Koltowska-
Haggstrom M, and Monson JP on behalf of the KIMS International Board Grov.1:h hormone (GH) replacement 
therapy in GH deficient adults: predictors of metabolic and clinical response Growth Hormone & IGF Research 
2007 17 ( 1 ): 67-76 doi: I 0.10 I 6/j.ghir.2006.1 I .002 Original paper 
43. (31) Monson JP, Jt>nsson P, Koltowska-Haggstrom M, Kourides I. Growth hormone replacement decreases 
serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor 
(statin) therapy Clinical Endocrinology, 2007 67 (4): 623-628, doi: I 0.111l/j.I365-2265.2007.02935.x 
original paper 
44. (32) Brabant G, Krogh Rasmussen A, Biller BMK, Buchfelder M, Feldt-Rasmussen U, Forssmann K, Jonsson 
B, Koltowska-Haggstrom M, Maiter 0 , Saller Band Toogood A, Clinical implications ofresidual GH 
response to provocative testing in adults with severe growth hormone deficiency Journal of Clinical 
Endocrinology & Metabolism 2007 92:2604-2609, Original paper 
45. (33) Peter Clayton, Helena Gleeson, John Monson, Vera Popovic, Stephen M Shalet, J Sandahl Christiansen 
Growth hormone replacement throughout life: Insights into age-related responses to treatment Growth 
Hormone & IGF Research 2007 17(5): 369-82 doi:J0.1016/j.ghir.2007.04.0 10 review 
46. (34) Michael Buchfelder, Peter Herbert Kann, Christian Wtister, Ulrich Tuschy, Bernhard Saller, Georg 
Brabant, Andrea Kleindienst, Panagiotis Nomikosland the German KIMS Board Influence of Growth Hormone 
Substitution Therapy in Deficient Adults on the Recurrence Rate of Hormonally Inactive Pituitary Adenomas: 
A Case-Control Study EJ E 2007 157 149-156 Original paper 
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47. (35) Hoybye C, JOnsson P, Monson JP, Kottowska-Haggstrom M, Hana V, Geffner M, and Abs R lmpact of 
the primary aetiology upon the clinical outcome of adults with childhood-onset growth hormone deficiency 
European Journal of Endocrinology 157: 589-596 Original paper 
48. (36) Meyer S, lpek M, Keth A, Minnemann T, von Mach MA, Weise A, Ittner JR, Nawroth PP, Plockinger 
U, Stalla GK, Tuschy U, Weber MM and Kann PH Short stature and decreased insulin-like growth factor 1 
(IGF-1)/growth hormone (GH)-ratio in an adult GH-deficient patient pointing to additional partial GH 
insensitivity due to a RI 79C mutation of the growth hormone receptor Growth Hormone and IGF Research 
17:307-3 14 Original paper 
49. (37) Gutierrez LP, Koltowska-Haggstrom M, Jonsson PJ, Mattsson AF, Svensson D, Westberg B, Luger A, 
Registries as a Tool in Evidence - Based Medicine: example of KlMS (Pfizer International Metabolic 
Database); Pharmacoepidemiology and Drug Safety 2008, 17:90-l 02 doi: 10.1002/pds. l 5 IO Original paper 
50. (38) Kottowska-Haggstrom M, Kind P, Monson JP, Jonsson B, Growth hormone replacement in hypopituitary 
adults with growth hormone deficiency evaluated by a utility-weighted quality of life index: a precursor to cost-
utility analysis Clinical Endocrinology 200868:122-129 doi: IO. I I 11/j.1365-2265.2007.03010.x Original 
paper 
51. (39) Mattsson A, Svensson D, Schuett B, Osterziel KJ and Ranke MB Multidimensional reference regions for 
IGF-1, IGFBP-2 and IGFBP-3 concentrations in serum of healthy adults Growth Honn lGF Res 2008 18:506-
516 
52. (40) Fideleff HL, Boquete HR, Stalldecker G, Giaccio AV, Sobrado PGV, Comparative results ofa 4 year 
study on cardiovascular parameters. Lipid metabolism, body composition and bone mass between untreated and 
treated adult growth hormone deficient patients Growth Horm IGF Res 2008 18 (4):318-324 
53. (4 1) Kreitschmann-Andermahr I., Poll EM, Reineke A, Gilsbach JM, Brabant G, Buchfelder M, FaBbender W, 
FaustM, Kann PH, Wallaschofski H Growth hormone deficient patients after traumatic brain injury - baseline 
characteristics and benefits after growth hormone replacement - an analysis of the German K!MS database 
Growth Hormone & /GF Research 2008 18, (6): 472-478 
54. (42) Abrams P, Boquete H, FideleffH, Feldt-Rasmussen U, Jonsson P.J, Koltowska-Haggstrom M, Wilton P, 
and Abs R Growth Hormone Replacement in Hypopituitarism Improves Lipid Profile and Quality of Life 
Independently of Changes in Obesity Variables Eur J Endocrinol 2008; 159: 825-832 doi: IO. I 530/EJE-08-
0448 
55. (43) Karbownik-Lewinska M, Lewinski A, McKenna S, Kokoszko A, Mucha S, Komorowski J, 
Krzyzanowska-Swiniarska B, Gryczynska M, Sowinski J, Junik R, Meads D, Koltowska-Haggstrom M, The 
Polish version of the Quality of Life Assessment of Growth Honnone Deficiency in Adults (QoL-AGHDA) -
four-stage translation and validation Polish J Endocrinol 2008 59 (5):374-384 
56. (44) Meyer S, Haist M, Schaefer S, Ivan D, Ittner JR, Nawroth PP, Plockinger U, Stalla GK, Tuschy U, Weber 
MM, Weise A, PfUtzner A, Habbe N, Kann PH. Association ofCOLIA I Sp I polymorphism with the effect of 
subcutaneously injected recombinant hGH in OH-deficient adults. Phannacogenomics. 2008Aug;9(8):I017-
26. 
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57. (45) Siyambalapitiya S, Jonsson P, Koltowska-Haggstrom M, Gaillard R, HoK, Ross RJM 
A cross-sectional analysis of testosterone therapies in hypopituitary men on stable pituitary hormone 
replacement. Clin Endocrinol 2009 90: 907-913 
58. (46) Moock J, Albrecht C, Friedrich N, Volzke H, Nauck M, Koltowska-Haggstrom M, Kohlmann T and 
Wallaschofski H Health-related quality of life and IGF-1 in growth hormone deficient adult patients on growth 
hormone replacement therapy: analysis of the German KIMS data and the Study of Health in Pomerania (SHIP) 
EurJ Endocrinol2009; 160: 17-24 
59. (47) Meyer S, Schaefer S, Ivan D, Stolk L, Arp P, Uitterlinden AG, Nawroth PP, PIOckinger U, Stalla GK, 
Tuschy U, Weber MM, Weise A, Pftltzner A, Kann PH. Growth hormone dose in growth hormone-deficient 
adults is not associated with IGF-1 gene polymorphisms Pharmacogenomics. 2009Feb;10(2):293-302. 
60. (48) Klose K, Jonsson B, Abs R, Popovic V, Koltowska-Haggstrom M, Saller B, Feldt-Rasmussen U, Kourides 
1 From isolated growth hormone deficiency to multiple pituitary honnone deficiency: an evolving continuum. A 
KIMS analysis Eur. J. Endocrinol .. 2009 Suppl 1 S75-S83 
61. (49) Koltowska-Haggstrom M, Mattsson A, Shalet S Assessment of quality of life in adult patieil1tS with growth 
hormone deficiency- KIMS® contribution to clinical practice and pharmacoeconomic evaluations Eur. J. 
Endocrinol., 2009 S5 l-S64 
62. (50) Thomas J Monson J Adult growth hormone deficiency throughout lifetime Eur. J. Endocrinol .. 2009 161: 
S97-SJ06 
63. (51) Verhelst J, Abs R Cardiovascular risk factors in hypopituitary growth hormone deficient adults Eur J 
Endocrinol 2009 161: S4 l-S49 
64. (52) Svensson J, Bengtsson B-A Safety aspects ofGH replacement Eur J 2009 161: S65-S74 
65. (53) Shalet S, Mukherjee A The value of lGF-1 estimation in adults with GHD Eur J Endocrinol 2009 161: 
S33-S39 
66. (54) Brabant G, Poll E, Jonsson p, Polydorou D, Kreitschmann-Andermahr !Etiology, baseline characteristics 
and biochemical diagnosis of GH deficiency in the adult: Are there regional variations? Eur J Endocrinol 2009 
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67. (55) Filipsson H, Johannsson G Growth hormone replacement in adults: interactions with other pituitary 
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