On-line NIS Registration System Austria A practical Guide in English

1. On-line NIS Registration System AustriaA practical Guide in English nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

2. Entering the system: www.basg.at 1. 2. 3. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

3. Welcome Page Edit existing NIS after having obtained password and NIS number Register new NIS, e.g. request password and NIS number Welcome The following registry constritutes the practical translation of the „National Regulation for the Reporting Obligations for Non-interventional Studies“, (Verordnung des Bundesministers für Gesundheit über die Meldepflicht von Nicht-interventionellen Studien), BGBl. II Nr. 180/2010. The responsibility for safeguarding the NIS Reporting Number and the password and the sharing of these details with third parties lies with the persons responsible for the NIS. Liability of the Federal Office for Safety in Healthcare (Bundesamt für Sicherheit im Gesundheitswesen, BASG) for any detriment resulting from the disclosure of access information is precluded. Should you have forgotten your password or should you want to deactivate and replace an existing password, a new password can be requested in an automated fashion, as long as the NIS number is known. The new password will be mailed to the e-mail(s) associated in the system with the persons registering and responsible for the NIS respectively. Should the e-mails have changed in the meantime, or in case the NIS reporting number and password have been replaced, please contact nis@ages.at nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

4. Welcome page - Help • Description of the functionalities of the NIS Registration System. Different functionalities are available depending on the NIS registration status. • Function „Neue NIS melden“ = Register new NISChoose this function to register a new NIS. Initially you are requested to enter contact information for the person registering the NIS and the person responsible for the NIS. Once this information has been submitted by pressing the „send“ button, an e-mail containing the NIS Registration number and matching password will be sent to the two e-mail addresses entered in the system. Password and NIS registration number are required to enter further information with the function „vorhandene NIS bearbeiten“ • Function „Vorhandene NIS bearbeiten“ = Edit existing NISChoose this function for data entry, updates and upload of documents. Please find in on the following slide a table listing the possibilities for updates for the respective fields • Function „NIS zurückziehen“ = Withdraw NISChoose this function to withdraw a NIS, which has been registered (without ethics vote), but is not yet visible in the public registry (21 day silent approval time). A withdrawal requires the entry of a justification. A withdrawn NIS can not be restarted at a later date, a new registration is required. • Function „NIS abbrechen“ = Prematurely terminate NISThis functionality is available only once the NIS is listed in the public registry, after successful registration and, where applicable the expiry of the 21 day silent approval. The premature termination of a NIS requires the entry of a justification. The applicant can choose to make the justification public or not, the termination will be visible in the public registry. A terminated NIS can not be restarted at a later date, a new registration is required. • Function „NIS beenden“ = End NISChoose this function to enter the date of the end for Austria (national NIS) or the global end of the NIS (multinational NIS). Should you fail to enter a date in either one of these fields, the allotted time for submission of the final reports will be based on the date initially entered upon registration for the „planned end of NIS“. The end of NIS will be visible in the public registry. • Function „NIS Abschlussbericht“ = NIS Final Report(s)Choose this function to upload the final report and the abbreviated final report for the NIS. The abbreviated final report will be made available to the public and the NIS will be listed as finalized. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

5. Flexibility of Fields nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

6. Screen 1: Information on Person registering the NIS Title First name (*… required field) Last name* Organisation Address* Post code* City* State* E-mail* back continue nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

7. Screen 2: Information on Person responsible for the NIS Title First name* (*… required field) Last name* Organisation Address* Post code* City* State* E-mail* Note: Fields will automatically be pre-filled with details of the person registering the NIS to facilitate data entry. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

8. On-line NIS Registration System Confirmatory e-mail: NIS-Number and Password Note: This e-mail will automatically be sent to the two e-mail addresses entered on screen 1 and screen 2. The „NIS-Meldenummer“ is the identifier of the Non-Interventional Trial when contacting the Agency. The automatically generated password cannot be modified, however, a new password can be requested for an existing NIS Number. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

9. Screen 3: Step 1 information entry into the registration system NIS number* Password* Enter Generate new password nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

10. Screen 4 - NIS definition according to §2a Abs 3 Austrian Medicines Act (AMG) Question 1: Are the medicinal products used prescribed in the usual manner in accordance with the terms of the marketing authorisation? * Question 2: Is the patient exposed to additional diagnostic or therapeutic measures beyond clinical routine? * Question 3: Is the patient exposed to any other additional measures? * Question 4: Is an observation and evaluation plan established? * Question 5: Does the treatment reflect the clinical routine? * Question 6: Is the decision to include the patient in the NIS clearly separate from the assignment to a particular therapeutic strategy? Is the therapeutic strategy decided prior to inclusion in the NIS? * Yes No nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

11. Additional Information • Help on fields on screen 3: • Definitions and Legal Framework • The Non-interventional Study is defined in § 2a para. 4 of the Austrian Medicinal Product Act. It represents the translation of Art 2c of Directive 2001/20/EC into National law. • Art 2c DIR/2001/20/EC • ‘non-interventional trial’: a study where the medicinal product(s) is (are) prescribed in the usual manner in accordance with the terms of the marketing authorisation. • 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 shall be applied to the patients and epidemiological methods shall be used for the analysis of collected data; • § 2a Para. 3 AMG: • „Nicht-interventionelle Studie“ ist eine systematische Untersuchung zugelassener Arzneispezialitäten an Patienten, sofern • die Arzneispezialität ausschließlich unter den in der Zulassung genannten Bedingungen verwendet wird, • die nicht-interventionelle Studie keine zusätzlichen diagnostischen oder therapeutischen Maßnahmen notwendig macht und keine zusätzlichen Belastungen des Patienten mit sich bringt, • und die Anwendung einer bestimmten Behandlungsstrategie nicht im Voraus in einem Prüfplan festgelegt wird, sie der medizinischen Praxis entspricht und die Entscheidung zur Verordnung der Arzneispezialität klar von der Entscheidung getrennt ist, einen Patienten in die Studie einzubeziehen. • Zur Analyse der gesammelten Daten werden epidemiologische Methoden angewendet. Nicht-interventionelle Studien sind entsprechend dem Stand der Wissenschaften zu planen und durchzuführen. • The requirement to use the prescribed medicinal product(s) in accordance with the terms of the marketing authorisation implies that its/their use is bound to the conditions of use outlined in the Summary of Product Characteristics (i.e. indication and contra-indications, dosing, mode of application,..). nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

12. Screen 5:Entry of Medicinal Products authorisation number Medicinal products according to § 89 AMG Are the medicinal products found in the codex of reimbursement according to § 31 3 Z 12 ASVG (Act on General Procedures) Add entry Empty list Back continue cancel Marketing authorisation number Marketing authorisation holder Codex of Reimbursement Tradename nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

13. Additional Information • Help on fields on screen 4: • The authorization number entered is checked against the list of national and European authorized products by the system. • Medicinal Products according to § 89 AMG: A transitional period is in place for medicinal products which were on the Austrian market on april 1st 1984 but not under a licensing obligation. Some of these products do not have an authorization number and can therefore only be entered via the list provided. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

14. Screen 6:Entry of further information Yes No Multinational NIS? * Is this NIS part of a post-marketing committment? * Commercial or academic (non-commercial) NIS? * Estimated number of patients * Average total honorarium per patient * Planned start date for Austria * Planned end of NIS * Opinion by an Austrian Lead-ethics committee? * Pos None Neg nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

15. On-line NIS Registration System – Errormessages Error, please correct fields (red !) No entry in Required field Value entered not acceptable nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

16. Screen 6:Entry of participants Add MD Add MD Add dentist Add pharmacist Add hospital Upload xml – see following slides Empty list Back continue cancel Note: Upon entering a post-code, city/village names will be prefilled. In certain cases, a further selection for political districts needs to be made. Please contact the agency when encountering difficulties nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

17. Screen 6:Upload of participants via xml File See: http://www.basg.at/arzneimittel/faq/nicht-interventionelle-studien/#c5762 Note: The upload of a structured xml file for participants can be performed via an XML-file and is practicable for NIS with a large number of participants. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

18. Screen 6:Upload of PDF documents Contract template / Justification Ethics opinion Observation and evaluation plan Add entry Note: Pdf-Dokuments are limited to 10 MB. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

19. Screen 6:Update/delete PDF documents Contract template Select Observation and evaluation plan Delete EC opinion (if “yes” earlier) nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

20. Screen 7:Review and submission • The information entered will be displayed on Screen 7 for review • Information will be submitted by clicking the button „send“ • Confirmation of submission will be sent to the two addresses listed in the information package, • ..including the PDF of the submitted information • ..in the form of an e-mail with attachment (see next slide) nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

21. On-line NIS Registration System Confirmatory e-mail nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

22. On-line NIS Registration System – End NIS Prematurely terminate NIS End NIS End in Austria (national NIS) Global end (multi-national NIS) Final reports already available? “x” for “yes” Note: The date of the end of NIS corresponds to either the end in Austria (for Austrian Studies) and the global end for multinational NIS. The timeline for submission of the final report and the abbreviated final report starts with the date entered. The end of NIS is notified in the public registry. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

23. On-line NIS Registration System –Upload final reports End in Austria (national NIS) Global end (multi national NIS) NIS abbreviated final report NIS final report NIS final report nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

24. NIS - Premature termination NIS premature termination NIS premature termination Justification Text to be made public? If yes, then „x“ Note: Premature termination is possible for all NIS published in the registry. A justification for the termination is required, but it is the applicant‘s choice of whether this text is made public. The status of premature termination is visible to the public. Once terminated, a later restart of the NIS is not possible. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

25. NIS - Withdrawal NIS Withdrawal Justification Note: Applicable only to NIS, which have been notified, but are not yet visible in the public registry. A justification for the termination is required. Once withdrawn, a later restart of the NIS is not possible. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

26. NIS Public Registry nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

27. How to enter the public NIS Registry 1. 2. 3. nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

28. NIS-Registry - Overview Note: The publicly available information can be downloaded as csv- or pdf-document. Information can be sorted via the column headers (Organisation, person responsible, duration, status) nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014

29. NIS-Registry – Detail view Abbreviated final report nis@ages.at L_INS_VIE_CLTR_I232_01 / Gültig ab: 02.06.2014