Observational Retrospective-prospective Study in Patients With Genitourinary Tumors Presenting COVID-19 Infection (SOGUG-COVID-19)
Conditions: Covid19, Genito Urinary Cancer
Sponsor: Spanish Oncology Genito-Urinary Group

 “RETROSPECTIVE-PROSPECTIVE OBSERVATIONAL 
 STUDY IN PATIENTS WITH GENITOURINARY TUMORS 
 THAT PRESENT COVID-19 INFECTION 
 (SOGUG-COVID-19).” 
 Sponsor: 
 Spanish Genitourinary Oncology Group (SOGUG) 
 Spanish Agency for Medicines and Health Products Code; AEMPS: 
 SOG-INM-2020-04 
 Short title: 
 Description of the population with genitourinary tumors and COVID-19. 
 Coordinators: 
 Dr. Miguel Angel Clement 
 Dr. Javier Puente 
 Dr. Natalia Vidal 
 Dr. Aránzazu González del Alba 
 Dr. Sergio Vázquez 
 Protocol version and date: 
 V1.2 from August 10, 2020 
 CONFIDENTIAL. SOG-INM-2020-04. Protocolo version 1.2 from August 10, 2020 
 Page  1  of  25 

 PROTOCOL SIGNATURE PAGE 
 Protocol  title:  “PROSPECTIVE  RETROSPECTIVE  OBSERVATIONAL  STUDY  IN 
 PATIENTS 
 WITH 
 GENITOURINARY 
 TUMORS 
 THAT 
 PRESENT 
 COVID-19 
INFECTION (SOGUG-COVID-19).”
 Protocol number: SOGUG-COVID-19 
 Protocol version: 1.2 from August 10, 2020 
 I  have  read  this  protocol  and  agree  to  conduct  this  study  in  accordance  with  all  provisions  of  the 
 protocol and in accordance with the Declaration of Helsinki. 
 REPRESENTATIVE OF THE SPONSOR: 
 Name: José Ángel Arranz 
 Position: President of SOGUG 
 Date and signature 
 COORDINATORS/CHIEF INVESTIGATORS 
 Name: Dr. Miguel Ángel Climent 
 Center: Valencian Institute of Oncology 
 Principal Investigator / Coordinator 
 Date and signature 
 Name: Dr. Javier Puente 
 Center: San Carlos Clinical Hospital in Madrid 
 Principal Investigator / Coordinator 
 Date and signature 
 Name: Dr. Natalia Vidal 
 Center: San Carlos Clinical Hospital in Madrid 
 Principal Investigator / Coordinator 
 Date and signature 
 Name: Aránzazu González del Alba 
 Center: Puerta del Hierro-Majadahonda University Hospital 
 Principal Investigator / Coordinator 
 Date and signature 
 Name: Sergio Vazquez 
 Center: Lucus Augusti University Hospital, Lugo 
 Principal Investigator / Coordinator 
 Date and signature 
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 INDEX 
 1. SUMMARY OF THE PROTOCOL 
 5 
 1.1. Administrative information 
 5 
 1.2. Methodological aspects 
 5 
 2. INTRODUCTION AND JUSTIFICATION OF THE STUDY 
 8 
 2.1. Justification 
 8 
 2.2. Background and current situation 
 9 
 2.2.1. Epidemiological aspects of the infection 
 9 
 2.2.2. Clinic associated with COVID-19 infection 
 10 
 2.2.3. Data reported in the oncology population 
 11 
 23. Working hypothesis 
 12 
 3. OBJECTIVES 
 12 
 3.1. Main objectives 
 12 
 3.2. Secondary objectives 
 13 
 4. STUDY METHODOLOGY 
 13 
 4.1. Study type and design 
 13 
 4.2. Study population 
 13 
 4.3. Inclusion criteria 
 14 
 4.4. Exclusion criteria 
 14 
 4.5. Study sample size 
 14 
 4.6. Sampling and recruitment method 
 14 
 4.7. Case definition 
 15 
 4.8. Data Logging 
 15 
 4.9. Study schedule 
 15 
 5. VARIABLES 
 16 
 5.1. Study variables 
 16 
 6. PROTECTION OF HUMAN SUBJECTS 
 17 
 6.1. Applicable legislation 
 17 
 6.2. Ethical supervision of clinical research 
 18 
 6.3 Informed consent 
 18 
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 6.4. Confidentiality 
 19 
 6.5. Funding source 
 20 
 7. ADMINISTRATION AND NOTIFICATION OF ADVERSE EFFECTS (AE) AND ADVERSE 
 REACTIONS (AR) 
 20 
 8. QUALITY GUARANTEE 
 21 
 8.1. Data consistency control 
 21 
 8.2. Quality control in the research center 
 22 
 8.3. Audits 
 22 
 9. DISCLOSURE PLAN AND COMMUNICATION OF RESULTS 
 22 
 9.1. Commitment and publication standards 
 23 
 10. BIBLIOGRAPHY 
 23 
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 1. SUMMARY OF THE PROTOCOL 
 EPA-AS POST-AUTHORIZATION OBSERVATIONAL STUDY 
 1.1. 
 Administrative Information 
 AEMPS study code: 
 SOG-INM-2020-04 
 Sending to the AEMPS: 
 April 22, 2020 
 Study title: 
 “RETROSPECTIVE-PROSPECTIVE  OBSERVATIONAL  STUDY  IN  PATIENTS  WITH 
 GENITOURINARY 
 TUMORS 
 THAT 
 PRESENT 
 COVID-19 
 INFECTION 
 (SOGUG-COVID-19).” 
 Abbreviation: 
 Description of the population with genitourinary tumors and COVID-19. 
 Reason for developing the study: 
 Sponsor initiative 
 Sponsor: 
 Spanish Genitourinary Oncology Group (SOGUG) 
 Sponsor contact address: 
 C/ Velázquez, 7, Planta 3 28001 Madrid 
 Clinical monitor: 
 MFAR Clinical Research S.L. 
 Clinical Monitor contact address: 
 Symphony 28, 2-1, 28054, Madrid. 
 1.2. 
 Methodological aspects 
 medical product of interest 
 Not applicable 
 First ethics committee to evaluate the study: 
 Autonomous CEIm of Galicia 
 Principal Investigators / Coordinators 
 Dr. Miguel Angel Clement  1 
 Dr. Javier Puente  2 
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 Dr. Natalia Vidal  2 
 Dr. Aránzazu González del Alba  3 
 Dr. Sergio Vázquez  4 
 Researcher/Coordinator Centers: 
 1  Valencian Institute of Oncology 
 2  San Carlos Clinical Hospital of Madrid 
 3  Puerta del Hierro-Majadahonda University Hospital 
 4  Lucus Augusti University Hospital, Lugo 
 Autonomous Communities of Researchers / Coordinators: 
 Valencian Community 
 Autonomous Community of Madrid 
 Galicia 
 Territorial scope: 
 National, Spain 
 Information source: 
 Medical records of the patients included after signing informed consent. 
 RETROSPECTIVE PART ONLY: medical records of patients included after signing 
 informed consent or waiver thereof in the cases contemplated (see 6.3 Informed consent). 
 Type of study (according to the AEMPS classification): 
 EPA-AS 
 Tracking Type:: 
 Ambispective (Prospective and retrospective). A 6-month follow-up is proposed for patients 
 in the prospective part. 
 Total number of patients expected to include: 
 They are expected to include  250, sufficient to respond  to the objectives set by the study. 
 Planned duration of the study: 
 Data collection  8 months. The estimated duration of  the project is 12 to 18 months, 
 depending on the patient inclusion rate. 
 Study duration for each participant: 
 No specific study visits will be carried out, other than obtaining informed consent in cases 
 where it is required. 
 Main objectives: 
 a)  Main objectives 
 i) 
 Describe  the  population  infected  by  COVID-19  with  genitourinary  tumors 
 (urothelial  cancer,  prostate  cancer,  testicular  cancer  and  renal  cancer)  treated  in 
 Spanish  hospitals,  know  the  clinical  presentation,  therapeutic  evolution  and 
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 prognosis  of  said  intercurrent  infectious  process,  as  well  as  its  possible 
 relationship with different clinical and therapeutic factors. 
 ii) 
 Assess  the  possible  relationship  of  the  different  oncological  treatments 
 administered  to  these  patients  with  the  clinical  evolution  of  COVID-19  infection, 
 considering  both  patients  who  have  undergone  oncological  treatment  previously, 
 during or after COVID-19 infection. 
 iii) 
 To  specifically  evaluate  the  impact of  COVID-19  infection  on  the  toxicity  of 
 immunotherapy 
 treatment 
 (mainly 
 pneumonitis) 
 and 
 the 
 impact 
 of 
 immunotherapy  on  the  evolution  of  the  infectious  condition  in  patients  with 
 tumors  of  genitourinary  origin,  in  three  different  scenarios:  during  treatment  , 
 after  treatment  and  in  patients  who  are  prescribed  treatment  after  the  infection 
 has passed. 
 iv) 
 Analysis  of  this  same  relationship  in  patients  with  genitourinary  tumors  and 
 asymptomatic COVID-19 infection with positive Ab serologies (IgM and IgG). 
 v) 
 To  evaluate  in  patients  with  Prostate  Cancer  (PCa)  the  impact  of  androgen 
 deprivation  therapy  (ADT)  and  new  antiandrogen  agents  (NAH)  with  or  without 
 corticosteroids on infection. COVID-19. 
 b)  Secondary objectives 
 i) 
 To  evaluate  the  mortality  associated  with  COVID-19  infection  in  the  population 
 with genitourinary tumors. Percentage of patients alive/dead at discharge. 
 ii) 
 To  evaluate  the  rate  (percentage)  of  complications  that  have  required  hospital 
 admission and/or ICU treatment. 
 iii) 
 Describe  the  frequency  of  asymptomatic  or  minimally  symptomatic  COVID-19 
 infections.  Percentage  of  asymptomatic  patients  or  with  mild  symptoms  included 
 in the study. 
 iv) 
 Evolution  of  the  oncological  disease.  Impact/influence  of  COVID-19  infection 
 on  the  effectiveness  of  oncological  treatment.  Data  will  be  collected  on 
 delays/modifications  in  follow-up  or  oncological  treatment  regimens.  The 
 average  delay  time  and  the  number  of  modifications  will  be  evaluated.  Likewise, 
 it  is  expected  to  obtain  data  on  time  to  progression  and  overall  survival  of  cancer 
 patients,  which  can  be  compared  with  the  reference  values  for  each  type  of 
 tumor pathology. 
 Main variables to evaluate (see section 5 of this protocol for more detail): 
 1.  Epidemiological 
 2.  Medical history 
 3.  Tumor pathology 
 4.  Immunotherapy treatment 
 5.  Current oncological treatment 
 6.  COVID-19 infection 
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 Number of researchers: 
 32 centers 
 Scope of application: 
 Spain 
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 2. INTRODUCTION AND JUSTIFICATION OF THE STUDY 
 2.1. Justification 
 We  are  immersed in  a  very  rapidly  evolving  pandemic  that  puts  patients  from  vulnerable 
 populations,  such  as  those  diagnosed  with  cancer,  at  significant  risk.  Clinical  data  on  COVID-19  in 
 cancer patients is limited and new information is published with each passing day. 
 Without  a  doubt,  a  more  accurate  understanding  of  these  risks  will  take  us  more  time  and,  for  now, 
 the  only  thing  we  can  do  is  educate  the  oncology  population  to  minimize  the  risks  of  infection  and 
 to seek healthcare in case of suspicious symptoms. 
 Currently  available  information  suggests  that  cancer  patients  are  at  higher  risk  of  infections,  serious 
 complications,  and  more  rapid  deterioration  from  COVID-19  than  other  patients.  (1)  .  However,  for 
 now  we  do  not  have  information  on  the  complications  associated  with  COVID-19  infection  and  the 
 systemic treatments used in these patients. 
 It  is  known  that  chemotherapy  causes  a  state  of  immunosuppression  in  cancer  patients,  associated 
 or  not  with  hematological  toxicity  secondary  to  most  chemotherapy  treatments.  The  more  or  less 
 pronounced  neutropenia  that  occurs  after  the  administration  of  different  chemotherapy  regimens 
 could  be  a  factor  that  is  related  to  a  greater  susceptibility  to  COVID-19  infection  as  well  as  a  higher 
 rate  of  complications.  It  could  also  be  that  the  frequency  of  complications  was  lower  because  the 
 immunological  storm  described  during  the  virus  infection  did  not  occur,  as  the  patient  did  not  have 
 a fully competent immune system. 
 Many  patients  with  prostate  cancer  receive  treatment  with  low-dose  corticosteroids,  with  the 
 intention  of  minimizing  the  toxicity  associated  with  them. Corticosteroids  have  a  hormonal, 
 anti-inflammatory  and  regulatory  role  in  patients'  immunity.  We  also  do  not  know  to  what  extent 
 these  prolonged  treatments  may  be  related  to  a  greater  predisposition  to  COVID-19  virus  infection, 
 the development of complications or a more aggressive evolution of the disease. 
 Some  organ  toxicities  secondary  to  immunotherapy  oncology  treatments  may  overlap  with 
 COVID-19  complications  (e.g.  pneumonitis,  which  causes  35%  of  toxic  deaths  caused  by 
 immunotherapy),  so  it  may  be  difficult  to  distinguish  whether  They  are  an  adverse  effect  of 
 immunotherapy,  a  complication  of  COVID-19  infection, or  a  combination  of  both.  Furthermore,  a 
 subgroup  of  patients  with  severe  COVID-19  infection  could  suffer  a  “cytokine  storm”  syndrome, 
 with  elevated  levels  of  IL-6,  IFN-γ  and  other  cytokines,  similar  to  secondary  hemophagocytic 
 lymphohistiocytosis  (sHLH),  induced,  although  infrequently,  due  to  viral  infections  (2,3)  .  In  this 
 scenario,  the  possibility  of  an  immunological  hyperreaction  due  to  immunotherapeutic  agents  and  a 
 possible  synergy  between  both  mechanisms  must  also  be  considered.  This  could  mean  a  higher  rate 
 of  patients  with  complications  from  the  viral  infection.  On  the  contrary,  immunotherapy  treatments 
 could  have  a  modulating  effect  on  the  immune  response  and,  to  a certain  extent,  protect  against the 
 “cytokine  storm”  condition,  which  is  the  one  most  closely  related  to  serious  complications  due  to 
 virus infection. 
 Treatments  with  antiangiogenic  tyrosine  kinase  inhibitors  (TKIs),  widely  used  in  patients  with 
 kidney  cancer,  also  have  a  role  in  regulating  immunity,  so  it  is  also  interesting  to  know  what 
 happens in these patients if they acquire the infection. coronavirus 
 2.2. Background and current situation 
 On  December  31,  2019,  the  Wuhan  Municipal  Health  and  Sanitation  Commission  (Hubei  Province, 
 China)  reported  a  cluster  of  27  cases  of  pneumonia of  unknown  etiology,  with  common  exposure  to 
 a  seafood,  fish,  and  animal  wholesale  market.  alive  in  Wuhan  city,  including  seven  serious  cases. 
 The  onset  of  symptoms  in  the  first  case  was  on  December  8,  2019.  On  January  7,  2020,  the  Chinese 
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 authorities  identified  a new  type  of  virus  from  the  Coronaviridae  family  as  the  causative  agent  of 
 the  outbreak,  which  has  subsequently  been  named  SARS-CoV.  2,  whose  genetic  sequence  was 
 shared  by  the  Chinese  authorities  on  January  12.  On  March  11,  the  WHO  declared  a  global 
 pandemic. 
 Coronaviruses  are  a  family  of  viruses  that  cause  infection  in  humans  and  a  variety  of  animals, 
 including  birds  and  mammals  such  as  camels,  cats  and  bats.  It  is  a  zoonotic  disease,  meaning  it  can 
 be  transmitted  from  animals  to  humans.  (4)  .  Coronaviruses  that  affect  humans  (HCoV)  can  produce 
 clinical  symptoms  that  range  from  the  common  cold  with  a  seasonal  pattern  in  winter  to  other  more 
 serious  ones  such  as  those  produced  by  the  Severe  Acute  Respiratory  Syndrome  (SARS)  and  of 
 Middle  East  Respiratory  Syndrome  (MERS-CoV)  (5)  .  Specifically,  SARS  in  2003  caused  more  than 
 8,000  cases  in  27  countries  and  a  fatality  rate  of  10%  and  since  then  it  has  not  been  detected  in 
 humans  again.  Since  2012,  2,499  cases  of  MERS-CoV  have  been  reported  in  27  countries 
 (although the majority of cases have been detected in Saudi Arabia), with a fatality rate of 34%. 
 2.2.1. Epidemiological aspects of the infection 
 As  in  other  outbreaks  caused  by  coronaviruses,  the  most  likely  primary  source  of  the  disease 
 caused  by  SARS-CoV-2  is  animal  origin.  At  this  time  it  seems  clear  that  the  reservoir  of  the  virus  is 
 the  bat,  while  research  continues  on  the  intermediate  host  animal,  with  controversy  between  the 
 pangolin  and  others.  How  the  virus  could  have  been  transmitted  from  the  animal  source  to  the  first 
 human  cases  is  unknown.  Everything  points  to  direct  contact  with  infected  animals  or  their 
 secretions.  In  studies  carried  out  in  animal  models  with  other  coronaviruses,  tropism  has  been 
 observed  for  the  cells  of  different  organs  and  systems,  mainly  producing  respiratory  and 
 gastrointestinal  symptoms.  (6)  ,  which  could  indicate  that  transmission  from  the  animal  to  humans 
 could  be  through  respiratory  secretions  and/or  material  from  the  digestive  system.  The  route  of 
 transmission  between  humans  is  considered  similar  to  that  described  for  other  coronaviruses 
 through  the  secretions  of  infected  people,  mainly  through  direct  contact  with  respiratory  droplets  of 
 more  than  5  microns  (capable  of  being  transmitted  over  distances  of  up  to  2  meters)  and hands  or 
 fomites  contaminated  with  these  secretions  followed  by contact  with  the  mucosa  of  the  mouth,  nose 
 or eyes  (7)  . SARS-CoV-2 has been detected in nasopharyngeal  secretions, including saliva. 
 2.2.2. Clinic associated with COVID-19 infection 
 In  the  longest  series  published  by  the  China  Center  for  Disease  Control,  describing  the 
 characteristics  of  all  cases  detected  in  mainland  China  from  the  beginning  of  the  outbreak  to 
 February  11,  2020  (72,314  cases),  1  .2%  of  cases  were  asymptomatic  (8)  .  These  cases  were  detected 
 in  the  context  of  exhaustive  searches  in  intrafamilial  outbreaks  (9)  and  some  ended  up  developing 
 symptoms  (10)  .  In  contrast,  on  the  Diamond  Princess  ship,  quarantined  in  Japan,  where  diagnostic 
 tests  were  carried  out  on  3,700  passengers,  50%  of  those  who  had  positive  results  were 
 asymptomatic.  (11,12)  .  Subsequently,  after  14  days  of  observation,  the  majority  developed  symptoms, 
 with  the  percentage  of  truly  asymptomatic  being  18%  (95%  CI:  15.5-20.2).  Asymptomatic  cases 
 are  more  frequent  in  children  and  it  has  been  observed  that  some  of  them  present  pulmonary 
 radiological  alterations,  such  as  multifocal  opacities  and  analytical  alterations,  such  as  elevated 
 phosphatase. 
 The  report  of  the  WHO  mission  to  China  describes  the  most  common  symptoms  and  signs  of 
 55,924  laboratory-confirmed  cases,  including:  fever  (87.9%),  dry  cough  (67.7%),  asthenia  (38.1%). 
 %),  expectoration  (33.4%),  dyspnea  (18.6%),  sore  throat  (13.9%),  headache  (13.6%),  myalgia  or 
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 arthralgia  (14.8%),  chills  (11  .4%),  nausea  or  vomiting  (5%),  nasal  congestion  (4.8%),  diarrhea 
 (3.7%),  hemoptysis  (0.9%),  and  conjunctival  congestion  (0.8%)  (13)  .  In  Europe,  with  14,011 
 confirmed  cases  reported  to  the  European  Surveillance  System  (TESSy)  by  13  countries  (97%  of 
 Germany),  the  most  frequent  symptoms  were:  fever  (47%),  dry  or  productive  cough  (25%),  sore 
 throat  (16%),  asthenia  (6%)  and  pain  (5%).  In  Spain,  with  18,609  reported  cases,  the  most  frequent 
 symptoms  were:  fever  or  recent  history  of  fever  (68.7%),  cough  (68.1%),  sore  throat  (24.1%), 
 dyspnea  (31%).  ,  chills  (27%),  vomiting  (6%),  diarrhea  (14%)  and  other  respiratory  symptoms 
 (4.5%) (49). Other symptoms related to different organs and systems have also been described: 
 - 
 Neurological:  in  a  study  with  214  patients  admitted  to  a  Wuhan  hospital,  36%  had  neurological 
 symptoms:  dizziness  (17%),  altered  level  of  consciousness  (7%),  stroke  (2.8%),  ataxia  (0  .5%) 
 and epilepsy (0.5%), hypogeusia (5.6%), hyposmia (5%) and neuralgia (2.3%)  (14)  . 
 - 
 Cardiological:  it  has  been  noted  that  sometimes  the  disease  can  present  with  symptoms  related 
 to  heart  failure  or  acute  myocardial  damage,  even  in  the  absence  of  fever  and  respiratory 
 symptoms.  (15)  . 
 - 
 Ophthalmological:  in  a  series  of  534  patients  confirmed  in  Wuhan,  dry  eye,  12.7%  blurred 
 vision,  11.8%  foreign  body  sensation  and  4.7%  conjunctival  congestion  (0.5%  presented  as  the 
 first symptom)  (16)  . 
 Seven  clinical  series  of  hospitalized  cases  have  been  published  in  China,  with  5,  41,  52,  99,  138, 
 1,099  and  72,314  cases  respectively.  The  most  frequent  symptoms  at  the  time  of  admission  in  all 
 series  are  fever,  asthenia  and  cough.  In  the  series  by  Wang  et  al. fever  was  the  most  common 
 symptom,  while  in  Guan  et  al.  It  is  noted  that  only  43.8%  of  the  patients  had  fever  at  the  time of 
 admission,  although  during  their  stay  in  the  hospital  the  vast  majority  develop  it.  (17,18)  .  Furthermore, 
 Yang  et  al.  refer  to  the  fact  that  11%  of  critically  ill  patients  did  not  have  fever  at  the  onset  of 
 symptoms  (19)  .  The  most  frequent  radiological  pattern  in  all  series  was  alveolar  infiltrate  (see  Table 
 1). 
 Table  1.  Clinical  characteristics  of  the  patient  series  of  Yang  et  al.,  Chen  et  al.,  Wang  et  al.  and 
 Guan et al. 
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 2.2.3. Data reported in the oncology population 
 Although  so  far  there  is  no  evidence  of  the  behavior  of  SARS-CoV-2  in  the  oncology  population,  it 
 is  possible  that  patients  undergoing  immunosuppressive  oncology  treatment  may  have  a  greater 
 susceptibility  to  it  and a  higher  incidence  of  associated  complications  than  the  general  population, 
 such as and as occurs with other respiratory viral infections such as the flu. 
 There  is  no  evidence  that  the  virus  worsens  the  tumor  pathology  itself  and  in  many  cases  it  has  a 
 mild  clinical  course.  However,  in  cancer  patients  it  could  be  associated  with  a  more  severe  clinical 
 picture,  the  severity  of  which  could  be  increased  if  other  factors  such  as  advanced  age  or  the 
 presence  of  other  comorbidities  are  associated.  This  increased  risk  of  complications  requires  strict 
 compliance  with  prevention  protocols  and  extreme  caution.  The  recommendations  made  to  avoid 
 contagion to the general population must be followed particularly strictly by cancer patients. 
 Several  overview  reviews  have  been  published  (especially  of  Chinese  and  Italian  experiences).  The 
 most  commented  article,  published  in  Lancet  Oncology  a  few  weeks  ago,  reveals  the  possibility 
 that  cancer  patients  have  a  worse  prognosis  when  suffering  from  COVID-19  (1)  ,  but  it  is  also  true 
 that  this  cohort  of  patients  had  a  higher  median  age  than  for  those  without  cancer  and  the 
 proportion  of  patients  is  so  small  that  there  may  be  great  heterogeneity  in  that  population  (cured  vs. 
 metastatic  patients,  etc.).  To  this  we  must  add  that  the  risk  for  cancer  patients  is  also  related  to  a 
 greater inability to receive necessary medical care. 
 Despite  this,  recently,  a  new  retrospective  review  has  been  published  in  Annals  of  Oncology  with 
 28  COVID-19  +  oncology  patients.  (20)  .  The  most  common  tumor  in  this  series  was  lung  cancer 
 (25%),  with  only  3  patients  with  genitourinary  cancer  (2  patients  with  prostate  cancer  and  1  patient 
 with  testicular  cancer).  The  median  age  was  65  years.  The  most  common  symptoms  were  fever 
 (82.1%)  and  cough  (78.6%),  and  the  most  common  laboratory  abnormalities  were  lymphopenia 
 (82.1%)  and  elevated  CRP  (82.1%).  The  risk  of  severe  complications  was  higher  in  patients  who 
 had  received  oncological  treatment  in  the  14  days  prior  to  the  diagnosis  of  the  infection,  with  an 
 HR  in  the  multivariate  analysis  adjusted  for  age  and  sex  of  4.079  (95%  CI  1.086-15.322,  p  0.037). 
 However,  despite  being  the  largest  series  collected  of  COVID-19+  oncology  patients,  it  has its 
 limitations,  which  are  mentioned  in  the  article  itself.  To  begin  with,  this  is  a  retrospective  study  of 
 28  patients.  Furthermore,  the  population  is  heterogeneous,  with  different  tumors  and  stages  (64.3% 
 are  stages  I-III),  which  is  not  taken  into  account  in  multivariate  analysis.  A  more  recent  article  in 
 Cancer  Discovery  with  69  patients  with  lung  cancer,  mainly  active  or  metastatic  (80%),  determined 
 that  previous  oncological  treatment  with  Programmed  Dead-1  (PD-1)  blockers  does  not  have  a 
 significant impact on severity of COVID-19 infection  (21)  . 
 23. Working hypothesis 
 The  identification  of  patients  with  genitourinary  tumors  who  suffer  from  infection  with  the 
 SARS-CoV-2  agent  can  represent  multiple  benefits  both  for  themselves  and  for  health  professionals 
 and  the  health  system  itself.  We  would  be  able  to  know  more  precisely  the  clinical  evolution  of  this 
 type  of  patient,  know  their  prognosis  and  be  able  to  select  the  most  appropriate  treatment  modality 
 for future pandemics. 
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 3. OBJECTIVES 
 3.1. Main objectives 
 ●  Describe  the  population  infected  by  COVID-19  with  genitourinary  tumors  (urothelial 
 cancer,  prostate  cancer,  testicular  cancer  and  renal  cancer)  treated  in  Spanish  hospitals, 
 know  the  clinical  presentation,  therapeutic  evolution  and  prognosis  of  said  intercurrent 
 infectious  process,  as  well  as  its  possible  relationship  with  different  clinical  and  therapeutic 
 factors. 
 ●  Assess  the  possible  relationship  of  the  different  oncological  treatments  administered  to 
 these  patients  with  the  clinical  evolution  of  COVID-19  infection,  considering  both  patients 
 who  have  undergone  oncological  treatment  previously,  during  or  after  COVID-19 
 infection. 
 ●  To  specifically  evaluate  the  impact  of  COVID-19  infection  on  the  toxicity  of 
 immunotherapy  treatment  (mainly  pneumonitis)  and  the  impact  of  immunotherapy  on  the 
 evolution  of  the  infectious  condition  in  patients  with  tumors  of  genitourinary  origin,  in 
 three  different  scenarios:  during  treatment  ,  after  treatment  and  in  patients  who  are 
 prescribed treatment after the infection has passed. 
 ●  Analysis  of  this  same  relationship  in  patients  with  genitourinary  tumors  and  asymptomatic 
 COVID-19 infection with positive Ab serologies (IgM and IgG). 
 ●  To  evaluate  in  patients  with  Prostate  Cancer  (PCa)  the  impact  of  androgen  deprivation 
 therapy  (ADT)  and  new  antiandrogen  agents  (NAH)  with  or  without  corticosteroids  on 
 infection. COVID-19. 
 3.2. Secondary objectives 
 ●  To  evaluate  the  mortality  associated  with  COVID-19  infection  in  the  population  with 
 genitourinary tumors. Percentage of patients alive/dead at discharge. 
 ●  To  evaluate  the  rate  (percentage)  of  complications  that  have  required  hospital  admission 
 and/or ICU treatment. 
 ●  Describe  the  frequency  of  asymptomatic  or  minimally  symptomatic  COVID-19  infections. 
 Percentage of asymptomatic patients or with mild symptoms included in the study. 
 ●  Evolution  of  the  oncological  disease.  Impact/influence  of  COVID-19  infection  on  the 
 effectiveness  of  oncological  treatment.  Data  will  be  collected  on  delays/modifications  in 
 follow-up  or  oncological  treatment  regimens.  The  average  delay  time  and  the  number  of 
 modifications  will  be  evaluated.  Likewise,  it  is  expected  to  obtain  data  on  time  to 
 progression  and  overall  survival  of  cancer  patients,  which  can  be  compared  with  the 
 reference values  for each type of tumor pathology. 
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 4. STUDY METHODOLOGY 
 4.1. Study type and design 
 This  is  a  national  multicenter,  observational,  retrospective  and  prospective  post-licensure  (EPA-AS) 
 study that will include patients with genitourinary tumors presenting with COVID-19 infection. 
 The  study  will  be  carried  out  in  Spanish  hospital  centers,  with  principal  investigators  belonging  to 
 the  medical  oncology  services  of  the  SOGUG  group  (Spanish  Genitourinary  Oncology  Group), 
 who  will  act  as  sponsor.  Once  the  patients  are  selected,  the  variables  described  in  section  5  of  this 
 protocol will be collected and studied. 
 The  study  will  use  data  obtained  from  the  patient's  medical  history,  with  no  plans  to  use  other 
 sources. 
 The  assignment  of  a  patient  to  a  specific  therapeutic  strategy  has  already  been  decided  in  advance 
 by  the  usual  clinical  practice  of  medicine;  The  decision  to  prescribe  a  specific  treatment  is  clearly 
 dissociated  from  the decision  to  include  a  patient  in  the  study.  No  intervention,  whether  diagnostic 
 or  follow-up,  will  be  applied  to  patients  other  than  standard  clinical  practice.  Epidemiological 
 methods will be used to analyze the data collected. 
 4.2. Study population 
 The  inclusion  of  a  total  of  250  patients  with  genitourinary  tumors  presenting  with  COVID-19 
 infection is expected, sufficient to respond to the objectives set by the study. 
 4.3. Inclusion criteria 
 - 
 Patients ≥18 years old. 
 - 
 Diagnosed with genitourinary cancer (urothelial, kidney, prostate and germ cell). 
 - 
 COVID-19 infection prior to oncological treatment, during treatment or after treatment. 
 - 
 COVID-19  infection  must  be  confirmed  by  PCR  or  serology,  regardless  of whether  or  not 
 the  patient  requires  hospitalization  due  to  the  infection.  Additionally,  clinical  and/or 
 radiological determination must be available in those patients who present symptoms. 
 4.4. Exclusion criteria 
 - 
 Not applicable. 
 As  this  study  is  an  EPA-AS,  all  the  researchers'  activities  are  carried  out  in  accordance  with  the 
 center's  usual  clinical  practice.  No  withdrawal  criteria  have  been  established.  Information  from  the 
 clinical  history  will  be  collected  as  long  as  it  does  not  exist  on  the  part  of  the  researcher.  patient 
 refusal  to  do  so.  Therefore,  those  patients  who  do  not  attend  the  corresponding  visits  will  be 
 declared  as  lost  to  follow-up,  those  patients  who  withdraw  their  consent  to  participate,  the  data 
 collected  up  to  that  point  will  be  used  for  statistical  analysis,  being  lost  to  follow-up  from  which  the 
 patient withdraws his consent. 
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 4.5. Study sample size 
 The  inclusion  of  a  total  of  250  patients  with  genitourinary  tumors  presenting  with  COVID-19 
 infection is expected, sufficient to respond to the objectives set by the study. 
 Given  the  characteristics  of  the  study,  the  total  number  of  patients  cannot  be  previously  calculated 
 accurately,  although  the  inclusion  of  approximately  250  patients  is  expected.  The  planned  analysis 
 is  the  descriptive  one  of  each  of  the  variables.  The  qualitative  variables  will  be  compared  with  each 
 other  using  the  Chi-square  test.  Quantitative  and  qualitative  analysis  using  Student's  T  analysis  or 
 ANOVA.  If  necessary,  the  corresponding  non-parametric  tests  will  be  applied.  Survival  will  be 
 calculated using Kaplan-Meyer curves and curve comparison using Log-Rank. 
 The  Statistical  Package  for  the  Social  Sciences  (SPSS)  will  be  used  for  statistical  analyses. 
 Additional analyzes could be performed with other statistical analysis packages. 
 4.6. Sampling and recruitment method 
 Patients  will  be  included  consecutively,  in  accordance  with  the  inclusion/exclusion  criteria 
 previously  established  in  sections  4.3  and  4.4  of  this  protocol.  Inclusion  will  be  carried  out 
 competitively without restrictions regarding the number of patients included in each center. 
 In  accordance  with  the  definition  of  the  study  population  and  disease  established  in  this  scientific 
 report,  patients  will  be  selected  from  the  diagnosed/treated  cases  of  genitourinary  tumors  presenting 
 with COVID-19 infection treated in the Spanish hospital centers participating in the study. 
 To  prevent  two  or  more  doctors  participating  in  the  trial  from  registering  the  same  case,  a 
 coordinator  is  designated,  who  controls  the  cases  included  in  his  center,  in  hospital  centers  with 
 several  participating  doctors,  and  preventive  measures  are  implemented  in  the  tool  that  controls 
 duplications. in the variables (such as age, sex, center or diagnosis). 
 4.7. Case definition 
 A  "case"  is  defined  as  any  patient,  diagnosed,  treated  or  followed  up  at  the  different  hospital  centers 
 where physicians authorized by the sponsor are informed, who meets the inclusion criteria. 
 Medical  care  will  be  provided  following  applicable  clinical  criteria,  in  the  context  of  routine 
 clinical  practice,  regardless  of  the  patient's  inclusion  in  the  study  and  following  the  best  judgment 
 of the specialists responsible for the patients. 
 4.8. Data Logging 
 Once  data  collection  is  possible  (when  the  patient  agrees  to  participate  in  the  study  through  the 
 informed  consent  procedure  detailed  in  point  6.3  of  this  protocol,  or  after  the  waiver  of  consent  has 
 been  requested  and  approved  (RETROSPECTIVE  PART  ONLY)  ,  medical  history  information  will 
 be  collected  to  obtain  the  necessary  data  and  complete  the  electronic  study  forms  designed  for  this 
 purpose. 
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 4.9. Study schedule 
 Study start date (Activation of the first center) 
 3Q 2020 
 End  date  of  the  study  (“Last  patient  last  visit” 
 or end of data extraction) 
 1T 2021 
 Study report completion date 
 2T 2021 
 Date of first publication 
 2Q 2021 (expected) 
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 5. VARIABLES 
 5.1. Study variables 
 A  data  collection  notebook  will  be  prepared  in  which  the  following  variables  will  be  collected  for 
 analysis: 
 Affiliation of the center: 
 ●  Hospital name 
 ●  Province 
 ●  Investigator's name 
 ●  Patient number 
 Patient characteristics: 
 ●  Age 
 ●  Sex 
 ●  Age 
 ●  Hospital  center  where  the  patient  is  recruited  (in  order  to  have  epidemiological  data  on  the 
 pandemic that may be of interest) 
 Pathological history: 
 ●  Concomitant pathology (cardiac, pulmonary, renal, liver, Diabetes Mellitus, HIV, AI) 
 ●  Usual pharmacological treatment 
 ●  Smoking and alcohol habit 
 Tumor pathology: 
 ●  Tumor type, histology and stage (initial and at diagnosis of infection) 
 ●  Date of cancer diagnosis 
 ●  Active cancer treatment or follow-up 
 ●  Participation in clinical trial 
 ●  Type  of  treatment  most  recently  received  for  the  infection  (Surgery;  Radiotherapy; 
 Chemotherapy:  Drug,  Immunotherapy,  TD:  Drug,  HT:  ADT  alone  or  with  Abiraterone, 
 Enzalutamide, others) 
 ●  Treatment lines 
 ●  Start and last dose received of the most recent oncological treatment 
 For patients with prostate cancer: 
 ●  Local treatment and type (Surgery, Radiotherapy) 
 ●  Adjuvant ADT or advanced disease (start date) 
 ●  NAH (date and line of treatment) 
 ●  Associated corticosteroid treatment: Prednisone vs Dexamethasone (dose) 
 COVID-19 infection data: 
 ●  Confirmation date of COVID-19 infection 
 ●  PCR diagnostic test 
 ●  IgG or IgM serological diagnostic test 
 ●  Present symptoms 
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 ●  Analytical alterations, lymphopenia, elevated CRP, high D-dimer. 
 ●  Thrombosis associated with COVID-19 infection 
 ●  Date of onset and disappearance of symptoms 
 ●  Days duration of fever and cough 
 ●  Radiological examination at the moment of greatest severity 
 ●  Complications of infection: presence of complications and/or hospital or ICU admission 
 ●  Admission date 
 ●  Date of most serious complication 
 ●  Treatments received for COVID-19 
 ●  Discharge status 
 ●  Fecha de high / exit 
 ●  Negativization of the presence of viruses by PCR 
 ●  Negative PCR date 
 For  patients  who  are  receiving  or  have  received  immunotherapy  treatments,  additional  information 
 will be collected: 
 ●  Immunotherapy treatment line 
 ●  Start/end date of immunotherapy treatment 
 ●  Date of last dose received prior to COVID-19 infection 
 ●  Immunotherapy received as monotherapy or combination 
 ●  Type of immunotherapy 
 ●  Adverse effects 
 Prospective follow-up data (6 months from patient inclusion): 
 ●  Date of start or restart of oncological treatment after infection 
 ●  Negative COVID-19 test prior to starting/restarting treatment 
 ●  Change/suspension of oncological treatment after COVID-19 
 ●  Surgery date in neoadjuvant patients 
 ●  Recurrence of COVID-19 
 ●  Best answer obtained 
 ●  Date of progression to oncological treatment 
 ●  Current status 
 ●  Last contact date 
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 6. PROTECTION OF HUMAN SUBJECTS 
 6.1. Applicable legislation 
 This  is  an  observational,  descriptive,  non-interventional  study  with  the  main  objective  of  collecting 
 information  on  patients  with  genitourinary  tumors  who  present  COVID-19  infection,  under  clinical 
 care and follow-up in the departments of participating centers distributed nationwide. 
 The  study  design  includes  the  collection  of  retrospective  and  prospective  data,  promoted  by  the 
 Spanish  Genitourinary  Tumors  Group  (SOGUG)  and  is  considered  of  public  interest.  Therefore,  in 
 accordance  with  Order  3470/2009  of  Health  and  Social  Affairs  (SAS),  of  December  16,  the 
 Sponsor  has  requested  the  EPA-AS  classification  from  the  AEMPS.  This  classification  has  been 
 ratified  by  the  AEMPS  on  April  23,  2020.  In  accordance  with  the  same  legislation,  the  participation 
 of  any  center  will  be  subject  to  the  approval  of  the  Post-authorization  Studies  Coordination 
 Committee,  a  favorable  opinion  from  a  Clinical  Research  Ethics  Committee  accredited  in  Spain 
 and the approval of the management of each participating center. 
 Participating  in  this  study  does  not  represent  any  additional  risk  for  patients  because  it  is  a  study 
 developed  from  information  recovered  from  the  clinical  history  and  clinical  evaluation  of  patients, 
 all  in  the  context  of  usual  clinical  practice  and  without  participation  of  the  patients.  patients  in  any 
 type  of  intervention  or  without  the  modification of  the  treatment  that  they  would  receive  if  they  had 
 not participated in the study. 
 This  protocol  will  be  carried  out  in  accordance  with  the  principles  adopted  by  the  18th  World 
 Medical  Assembly  (Helsinki,  1964)  and  its  subsequent  amendments  (Fortaleza,  2013),  following 
 the rules of good clinical practice and the code of ethics. 
 6.2. Ethical supervision of clinical research 
 The  study  will  initially  be  submitted  for  evaluation  by  the  Autonomous  CEIm  of  Galicia .  As 
 detailed  in  section  6.1,  the  study  will  also  have  the  corresponding  and  applicable  authorizations  in 
 accordance  with  the  regulations  of  each  center  and  the  guidelines  of  Order  3470/2009  SAS  of 
 December 16. 
 6.3. Informed consent 
 All information  will  be  extracted  from  the  medical  records  of  participating  patients  who  have 
 authorized  its  use  by  signing  the  informed  consent.  All  patients  included  in  the  prospective  part  of 
 the  study,  upon  authorization  by  the  competent  authorities,  must  sign  an  informed  consent  prior  to 
 their  inclusion  in  the  study  that  authorizes  the  use  of  the  information  contained  in  their  medical 
 records. 
 RETROSPECTIVE  PART  ONLY:  In  all  cases  where  it  is  possible  for  the  patient  to  sign  informed 
 consent,  it  will  be  collected.  Due  to  the  nature  of  the  study  and  in  order  not  to  generate  information 
 bias  in  those  patients with  a  worse  prognosis  who  have  not  been  able  to  overcome  the  disease, 
 exemption  from  informed  consent  is  contemplated  for  patients  who  have  died  in  the  retrospective 
 part of the study. study, prior to authorization of the study by the competent authorities. 
 RETROSPECTIVE  PART  ONLY:  The  local  Ethics  Committee  must  approve  the  absence  of  written 
 authorization  by  signing  the  informed  consent  (as  established  by  local  Spanish  regulations:  SAS 
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 Order  3470/2009).  It  is  possible  to  dispense  with  the  request  for  informed  consent  of  patients  who 
 have  died  prior  to  the  authorization  of  this  study  by  the  competent  authorities  provided  that  a  prior 
 refusal  has  not  been  obtained  for  the  signing  of  the  informed  consent  by  of  the  patient  or  a 
 revocation  thereof.  On  the  other  hand,  this  methodology  has  been  proposed  taking  into  account 
 that: 
 ●  There  are  no  studies  on  the  involvement  of  COVID  in  patients  affected  by  the  disease 
 under study 
 ●  The  high  incidence  of  fatal  cases  leads  to  the  need  to  collect  these  cases  in  order  not  to 
 cause  bias  in  the  sample  due  to  relevant  loss  of  patients  that  generates  serious  problems  of 
 representativeness of the population under study and scientific validity. 
 For  all  patients,  whether  or  not  they  have  signed  informed  consent,  the  data  are  included  in  the 
 study  in  an  anonymized  and  dissociated  form,  ensuring  that  they  cannot  be  associated  with  any 
 identified  or  identifiable  person.  The  researcher  will  assign  each  patient  included  in  the  study  a 
 numerical  code  with  which  said  patient  will  be  identified  during  the  study.  The  code  will  not 
 contain  personal  information  and  no  other  data  that  allows  patient  identification  will  be  collected 
 during  the  study.  The  use  of  patient  data  will  be  subject  to  a  commitment  to  confidentiality  by  all 
 personnel  participating  in  the  study,  including  the  researcher  and  his  collaborators,  data  managers, 
 data  analysts,  and  monitors;  this  should  be  properly  recorded  in  the  patient's  medical  record,  with 
 specific  reference  to  the  SOGUG-COVID-19  study.  The  researchers  participating  in  the  study 
 undertake  not  to  identify  or  carry  out  re-identification  tasks  that  compromise  the  anonymity  of  the 
 patients included in the study. 
 The  data  will  be  recorded  using  the  Electronic  Data  Capture  software  owned  by  MFAR  S.L.,  which 
 is  developed  and maintained  in  strict  compliance  with  regulatory  standards  for  electronic  digital 
 capture  systems  for  clinical  data.  All  EDC  forms  are  designed  according  to  the  eCRF  defined  by 
 the study protocol. 
 All database  users  are  uniquely  identified  by  name,  all  access  to  the  software  is over  a  secure, 
 encrypted  connection,  and  all  activities  are logged  and  audited.  Only  SOGUG  (the  study  sponsor) 
 and MFAR (the CRO with delegated functions) will have access to the data. 
 6.4. Confidentiality 
 In  accordance  with  the  Organic  Law  on  the  Protection  of  Personal  Data  (Organic  Law  3/2018,  of 
 December  5,  on  the  Protection  of  Personal  Data  and  guarantee  of  digital  rights  -  LOPD),  the 
 sponsor  guarantees  the  adoption  of  the  necessary  measures  to  guarantee  confidentiality  in  the 
 processing of personal data. 
 Only  the  reporting  physicians  (principal  investigators  participating  in  the  study)  will  know  the  full 
 name  of  their  patients.  No  confidential  information  unnecessary  for  the  intended  purposes  of  the 
 study is collected. 
 An  electronic  platform  will  be  used  to  record  data  in  the  Electronic  Case  Report  Form  (eCRF).  To 
 access  the  application,  users  must  identify  themselves  with  a  username  and  password  strictly  for 
 personal  use.  Each  reporting  doctor  will  only  have  access  to  the  data  he/she  submitted  that  is 
 strictly  necessary  for  the  work.  Any  document  containing  identification  data  will  remain  in  the 
 center at all times, without being included in the database. 
 The  data  will  be  collected  in  a  research  file  under  the  responsibility  of the  sponsor  and  will  be 
 processed  within  the  framework  of  the  study,  ensuring  that  the  sponsor  will  adopt  the  relevant 
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 measures  to  guarantee  compliance  with  current  legislation  on  data  protection  in  all  cases.  The 
 encrypted  data  may  be  transmitted  to  third  parties  and  other  countries,  but  in  no  case  will  it  contain 
 information  that  can  directly  identify  any  patient,  such  as  name  and  surname,  initials,  address  or 
 social  security  number,  among  others.  If  this  transfer  occurs,  it  will  be  for  the  same  study  purposes 
 as  those  described  above  or  only  for  scientific  publications,  but  always  maintaining  patient 
 confidentiality in accordance with current legislation. 
 The  database  will  be  examined  exclusively  by  the  scientific  and  medical  staff  of  the  sponsor.  No 
 personal  data  or  any  information  that  may  be  related  to  patients  will  be  included  in  this  database. 
 The  database  administrator,  data  manager  and  monitor  (if  applicable)  will  have  access  to  all  data 
 that is not linked to any identifiable person. 
 In  data  explorations  carried  out  by  researchers  authorized  by  the  Scientific  Committee  and  in 
 international  data  transfers  to  International  Registries,  if  applicable,  patients  will  be  identified by  a 
 numerical  code  assigned  automatically  and  randomly  by  the  computer  application  at  the  beginning 
 of  the  registry.  each  case  to  maintain  the  confidentiality  of  the  patient's  personal  data,  as  established 
 in  the  General  Data  Protection  Regulation  2016/679  of  the  Parliament  and  of  the  Council  of  the 
 European Union (EU) on April 27, 2016. 
 Access  to  the personal  information  of  the  study  subjects  will  be  restricted  to  the  doctor/study 
 collaborators,  the  health  authorities  (Spanish  Medicines  Agency),  the  Clinical  Research  Ethics 
 Committee  and  the  personnel  authorized  by  the  sponsor,  when  they  need  to  evaluate  the  data.  and 
 study procedures, but always maintain patient confidentiality in accordance with current legislation. 
 This  evaluation  will  be  carried  out  in  the  presence  of  the  main  researcher  or  collaborators, 
 responsible  for  guaranteeing  the  confidentiality  of  the  data  in  the  medical  records  of  the  study 
 subjects.  Only  the  data  collected  for  the  study  will  be  transmitted  to  third  parties,  with  at  least  the 
 level  of  protection  of  the  current  legislation,  including  the  transfer  of  data  outside  the  area  of 
 application of the reference legislation. 
 6.5. Funding source 
 The  study  sponsor  funds  the  study  according  to  the  guidelines  of  this  protocol.  This  funding  covers 
 all  research  materials;  the  cost  of  registration  and  control  processes  in  ethics  committees  and  health 
 authorities;  the  design,  maintenance  and  management  of  the  database;  eventual  statistical 
 consultations,  if  necessary;  and  publication  and  reporting  costs.  The  financing  will,  in  any  case,  be 
 independent of the results of the study. 
 The  board  of  directors/scientific  committee  of  the  sponsor  guarantees  non-interference  in  the  case 
 selection  processes,  data  analysis  or  in  any  other  process  that  may  affect  the  results  of  the  study  that 
 involve the exploration and presentation of data. 
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 7. REPORTING OF ADVERSE REACTIONS (AR) 
 In  accordance  with  the  provisions  of  section  8.3  of  Order  SAS/3470/2009,  of  December  16,  which 
 publishes  the  guidelines  on  observational  post-authorization  studies  for  medicines  for  human  use, 
 for  studies  classified  as,  EPA-  AS  they  are  considered  prospective  monitoring,  suspicions  of  serious 
 adverse  reactions  that  are  detected  during  the  course  of  the  study  will  be  notified  to  the  contact 
 point  designated  by  the  competent  body  in  matters  of  pharmacovigilance  of  the  autonomous 
 community  where  the  health  professional  who  carries  out  his  or  her  activity.  notify  the  case,  within 
 a  maximum  period  of  15  calendar  days  from  when  you  became  aware  of  the  suspected  adverse 
 reaction. 
 In  the  event  that  the  sponsor  is  a  group  of  professionals  (as  is  the  case  of  SOGUG),  you  may 
 choose  one  of  the  following  two  options:  1)  yellow  card  to  the  corresponding  autonomous 
 pharmacovigilance  center,  indicating  in  observations  the  name  and  code  of  the  study  from  which  it 
 comes;  or  2)  use  the  online  upload  through  the  SINAEM  portal  of  the  AEMPS,  following  the 
 instructions published by the AEMPS (this second option is the recommended one). 
 For  this  study,  the  research  team  will  make  notifications  of  serious  adverse  reactions  to  the  Sponsor 
 within 24 hours after having become aware of: 
 MFAR Clinical Research, S.L.  by fax (+ 34 93 253 11 68) or 
 e-mail:  investigacion@mfar.net 
 MFAR  will  act  as  recipient  of  the  notifications  that  it  will  manage  with  the  Sponsor  and  after 
 receiving  approval  from  the  Sponsor,  it  will  notify  the  competent  bodies  of  each  Community  in 
 matters of pharmacovigilance, when appropriate. 
 The  accumulated  data  on  safety  aspects  (serious  adverse  events  and  adverse  drug  reactions)  related 
 to  medical  products  subject  to  study  will  be  recorded  in  the  eCRF  and  will  be  included  by  the 
 sponsor  in  the  clinical  study  report,  since  this  study  is  based  on  the  use  secondary  data,  an 
 expedited report to the sponsor is not required. 
 In  addition  to  the  details  specified  in  the  previous  paragraph,  any  relevant  safety  finding  detected 
 during  the  study  will  be  reported  to  the  AEMPS  and  the  competent  bodies  of  the  autonomous 
 communities involved, regardless of the design or type of study. 
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 8. QUALITY GUARANTEE 
 8.1. Data consistency control 
 The  investigator  or  designated  responsible  person  is  responsible  for  recording  and  verifying  the 
 accuracy of subject data. 
 The  study  will  use  an  online  data  collection  notebook  (eCRF).  Designated  CRO  staff  will  review 
 the  data  collected  by  research  staff  for  completeness  and  accuracy,  in  accordance  with  the 
 monitoring  plan  agreed  upon  with  the  Sponsor.  Electronic  data  queries  indicating  the  nature  of  the 
 findings  and  requesting  clarification  for  discrepancies  and  missing  values  will  be  created  and sent 
 to  the  research  center  via  an  electronic  data  capture  (EDC)  system.  Designated  staff  at  the 
 investigator's  site  are  required  to  respond  promptly  to  inquiries  and  make  any  necessary  changes  to 
 the data. 
 Concomitant  treatments  and  all  drug  information  entered  into  the  database  will  be  coded  using  the 
 WHO  Drug  Reference  List,  which  employs  the  Anatomical  Therapeutic  Chemistry  classification 
 system. 
 Medical  history/current  medical  conditions  and  adverse  events  will  be  coded  using  the  NCI 
 CTCAE  V  5.0  guidelines  and  the  Medical  Dictionary  for  Regulatory  Activities  Terminology 
 (MedDRA). 
 Facility  staff  designated  by  the  investigator  will  enter  the  information  required  by  the  protocol  into 
 the eCRFs as well as the CRO-designated application form. 
 8.2. Quality control in the research center 
 Prior  to  the  start  of  the  study,  the  protocol  and  CRFs  will  be  reviewed  with  the  investigators  and 
 their staff via a site initiation telephone visit. 
 During  the  study,  a  monitor  will  contact  selected  sites  through  remote  monitoring  visits  to  verify 
 the  integrity  of  patient  records  and  the  accuracy  of  entries  in  the  CRFs.  Key  study  personnel  should 
 be available to assist the field monitor during these visits. 
 The  investigator  must  maintain  source  documents  for  each  patient  in  the  study,  which  consist  of 
 case  and  visit  notes  (medical  records  from  hospitals  or  clinics)  containing  demographic  and 
 medical  information,  laboratory  data,  electrocardiograms,  and  the  results  of  any  other  tests  or 
 assessment. 
 All  information  recorded  in  the  CRFs  must  be  traceable  to  the  source  documents  in  the  patient  file. 
 The  investigator  must  also  retain  the  original  signed  informed  consent  form  (a  signed  copy  is  given 
 to the patient). 
 The  researcher  must  give  the  monitor  access  to  all  relevant  source  documents  to  confirm  their 
 consistency with the entries in the CRF. 
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 8.3. Audits 
 To  ensure  data  quality,  study  integrity,  and  compliance  with  the  protocol  and  various  applicable 
 regulations  and  guidelines,  the  sponsor  may  conduct  visits  to  the  institutions  participating  in  the 
 studies. 
 The  investigator,  by  agreeing  to  participate  in  this  protocol, agrees  to  cooperate  fully  with  any 
 quality  assurance  visits  conducted  by  third  parties,  including  representatives  of  the  sponsor, 
 national  regulatory  authorities,  as  well  as  to  allow  direct  access  to  documentation  related  to  the 
 clinical  trial.  (including  CRFs,  source  documents,  hospital  patient  records,  and  other  study  files)  to 
 such authorized persons. 
 The  investigator  must  inform  the  sponsor  immediately  in  case  a  regulatory  authority  inspection  is 
 scheduled. 
 9. DISCLOSURE PLAN AND COMMUNICATION OF RESULTS 
 The  study  sponsor  has  the  rights  to  explore  the  collected  data,  store  and  protect  it,  and  acts  as  a 
 Scientific  Committee  for  the  approval  of  proposals  for  data  exploration  and  publication  of  the 
 results carried out by the researchers. 
 The  objective  of  the  study,  openly  epidemiological,  is  to  collect  information  on  the  management  of 
 the  study  disease  in  different  participating  hospitals  to  establish  a  framework  of  action  (usual 
 practice) and, therefore, study options for the management of the disease beneficial to the patients. 
 9.1. Commitment and publication standards 
 The  coordinating  researchers  and  the  sponsor  are  responsible  for  the  preparation  of  manuscripts, 
 abstracts,  posters,  etc.  that  summarize  the  recorded  data  for  publication.  The  global  data  will  be 
 used  in  documents  sent  for  publication  to  conferences  and  medical  journals,  mentioning  the  study 
 and the sponsor. 
 Regarding  the  authorship  policy  of  publications,  the  rules  and  SOPs  of  the  sponsor  (SOGUG)  will 
 be followed. 
 The anonymity of the data source subjects will be maintained at all times. 
 The  results  or  conclusions  of  the  study  will  be  communicated  mainly  in  scientific  publications 
 before being disseminated to the non-health public. 
 Participating  investigators  should  not  publish  any  patient  data  that  is  directly  related  to  the  study 
 objectives until the trial report is published. 
 The  sponsor,  SOGUG,  undertakes  to  deliver  the  monitoring  reports  and  the  final  report  to  the 
 competent bodies of the CCAA in a timely manner, following current regulations. 
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