Economic Contract to Conduct a Post-Authorisation Observational Drugs Study

CONTRACT Nº HUVM/201_EP/_____

ECONOMIC CONTRACT TO CONDUCT A POST-AUTHORISATION OBSERVATIONAL DRUGS STUDY

In ______, on __ of __ of ______

BY AND BETWEEN

Details of the hospital at which the study will be conducted

(Fill out as many hospitals as are included in this contract)

Details of the R&D&i managing body of the hospital (hereinafter, the "managing body")

Details of the sponsor

If applicable, details of the contract research organization or body acting on behalf of the sponsor (hereafter, “CRO/body”)*

*Attached is a certificate from the sponsor authorizing the CRO/body to act on its behalf

The appearing parties declare that they fulfil the necessary conditions to enter into this contract and hereby make the following

RECITALS

I.- ______(name of sponsor) acts as the sponsor of a post-authorization observational study (hereinafter, the "study") to be conducted at the ______, ______, ______and ______(name of the hospital at which the study is to be conducted), in ______, (city in which the hospital is located), pursuant to the provisions of Act 29/2006, of 26 July, on guarantees and rational use of medicines and medical devices; Royal Decree 577/2013, of 26 July, regulating pharmacovigilance of medicines for human use; Order SAS/3470/2009, of 16 December, establishing guidelines on post-authorization observational studies of medicines for human use; the Declaration of Helsinki, in its current version; the standards of good clinical practice, the standards of the International Conference on Harmonization, known by its acronym ICH; and Decree 439/2010, of 14 December, regulating the bodies of health care ethics and biomedical research in Andalusia, whose details are:

- Title: ______.

- Protocol Code: ______.

Clarifying Note: Without prejudice to the internal code of the protocol of each sponsor, all protocols for post-authorization studies must be identified by a 12-digit code using the following coding standards: Positions 1-3: first three letters of the sponsor. Positions 4-6: first three letters of the active ingredient being studied, one of them if there are more than one. Positions 7-10: current year. Positions 11-12: 2-digit sequential number, the number of the study being conducted that year for that active ingredient. Only one code shall be assigned per protocol. If the same study is to be performed in 4 Autonomous Communities, it shall be identified by the same code in all of them.

- Monitor: ______, with NIF: ______.

Clarifying Note: In the event that there is a monitor on the study, if on the contract signing date the identity of the monitor is not known, the name of the body responsible for monitoring the study must be indicated, where appropriate, with the sponsor being required to notify this identity as soon as it has been determined.

• Hospital: (Fill out as many hospitals as are included in this contract)

- Lead researcher: Dr. ______, with NIF: ______.

- Department or Clinical Management Unit: _______.

- Collaborators: Mr./Ms. ______, with NIF: ______.

The study shall be conducted according to the contents of the protocol authorized by the competent body of the Ministry of Health, Social Services and Equality (for PAS-LA and PAS-AS) or of the Autonomous Community (for PAS-FU).

PAS-ODs and No-PAS do not require such authorization, in accordance with Order SAS/3470/2009, of 16 December, meaning that they shall be conducted in accordance with the protocol approved by the relevant Research Ethics Committee.

The study has received the favourable evaluation, dated __ of __ of ______20__, of the Committee ______(name, province and autonomous community of the Research Ethics Committee), accredited in accordance with applicable regulations.

According to the protocol, the study expects to include at this hospital an estimated number of ______participants.

II.- The aim of post-authorization observational studies is to compile additional information regarding the effects of the drugs, and the characteristics associated with their use in the conditions approved in the technical file, or under normal conditions of use, in order to complement the information obtained during Phases I, II and III and contribute to their best use.

In the case of non-interventional post-authorization studies (NO-PAS), such studies involve investigating critical exposure factors that are not the drugs themselves.

III.- The parties agree to conduct the study ensuring maximum respect for ethical principles and promoting the effective control mechanisms thereof. The parties shall also ensure the prevention of any dishonest conduct during the implementation of the study. Insofar as the sponsor is subject to the Foreign Corrupt Practices Act, known by its acronym FCPA (Foreign Corrupt Practices Act, approved in 1977 by the Congress of the United States of America), the parties shall ensure compliance therewith.

And therefore they agree to formalize this agreement according to the following:

CLAUSES

ONE.- OBJECT

This contract is intended to establish the commitments to be assumed by the undersigned parties in relation to the implementation of the study referred to in Recital I.

TWO.- OBLIGATIONS

A) The sponsor agrees to comply with the obligations in paragraph 6.1 of the Annex to the Order SAS/3470/2009, of 16 December, regarding the conduct of the study. Similarly, in connection with this contract, it undertakes to:

- Provide the necessary documentation.

- Pay the amounts accrued under the study.

- Respect the confidentiality of the information relating to the study and guarantee the anonymity of the participants.

B) The hospital undertakes to:

- Ensure the study is conducted properly.

- Respect the confidentiality of the information relating to the study and guarantee the anonymity of the participants.

C) The managing body undertakes to carry out the economic and administrative management of the study in accordance with the Cooperation Agreement signed between the Andalusian Health Service and the R&D&i Manager Foundations of the Andalusian Public Health System in 2012.

The researcher declares that on the signing date of this contract there are no plans, during the course of the study, to conduct any clinical practice in addition to that contemplated within the normal conditions of clinical practice. If it is ultimately necessary to conduct additional clinical practice, this shall be subject to the provisions in the following clause regarding the costs incurred.

THREE.- FINANCIAL COMPENSATION

The cost of conducting the study at the hospital was initially budgeted at EUR ______(insert the total amount in figures). As compensation for running the study, the sponsor shall pay the sum accrued as a result of the execution thereof plus any applicable indirect taxes, according to the breakdown provided below, the details of which are also contained in the economic report and in the visits and potential allowances breakdown which are attached to this contract as Annexes 1 and 2, respectively (only Annex 1 should be completed for No-PAS studies), hereinafter forming an inseparable part thereof:

1. For the administrative management: EUR 1.088,63

2. For indirect costs, 30% of the budget set for each participant in the study, resulting from the hospital's application of the cost of the study: EUR ______for each participant recruited (insert the amount for indirect costs for each participant in figures), representing a total of EUR ______(insert the total amount for indirect costs in figures), corresponding to the total number of participants expected to be included in the study. The resulting amount shall be used for activities to support research, development and innovation at the health hospital, preferably in support of clinical research.

3. For compensation to the research team (lead researchers and collaborators stated in the study protocol), 35% of the estimated budget for each participating subject, EUR ______per evaluable participant recruited who completes the study according to the protocol (insert the amount as compensation to the research team for each participant in figures), representing a total of EUR ______(insert the total amount as compensation to the research team in figures), corresponding to the total number of participants expected to be included in the study. The compensation for the participants who do not complete the study is described in detail in the economic report attached to this contract.

4. To promote R&D&i (this shall be applied by the management of the hospital in accordance with the objectives established within the program contract or in the relevant contracts for the management of the clinical management units, and shall be aimed at promoting the R&D&i of the clinical management units or the departments at which the researchers run the study), 35% of the calculated budget for each participating subject, EUR ______(insert amount for promoting R&D&i for each participant in figures) per evaluable participant recruited who completes the study according to the protocol, representing a total of EUR ______(insert the total amount for promoting R&D&i in figures), corresponding to the total number of participants expected to be included in the study. The compensation for the participants who do not complete the study is described in detail in the economic report attached to this contract.

Given that this is a study that is conducted in accordance with normal conditions of clinical practice, it is not expected to generate any extraordinary direct costs. The following are considered extraordinary direct costs: any expenses that would not have occurred in the absence of participants in the study, such as additional analyses and complementary examinations, changes in the duration of care to the participants, reimbursement of expenses to the participants, equipment purchases or participant compensation. In the event that such costs are generated within the routine clinical practice, they shall be valued at the prices set by the regulation establishing the public prices of health services provided by dependent and associated hospitals belonging to the Andalusian health system, and they shall be specified in the relevant economic report.

The reimbursement for expenses or compensation to the participants, as appropriate, shall be made after submission of the supporting receipts/invoices to the manager of the study.

FOUR.- MODIFICATIONS

Any amendments that do not have economic repercussions shall be notified to the competent bodies by attested means, as well as to the hospital and managing body, with it being unnecessary to formalize any additional clause or document to this contract.

In cases where the changes involve an economic impact, they must be accepted by all the parties, and the official economic report template must be filled out, to reflect the items and amounts, which shall be appended to the body of the contract and the previously signed report, thereby forming an essential part of the contract. This updated economic report will not replace the previous one, but rather it shall be considered a complement thereto.

FIVE.- PAYMENTS

The amounts outlined in the foregoing clauses shall be paid by the sponsor as follows:

a) The total amount of the administrative management shall be paid upon the signing of this contract, and in no case shall it be refundable.

The managing body in studies whose economic report is zero euros (€ 0), sponsored by non-profit institutions or researchers from the Public Health System, may waive the payment of the amount derived from the administrative management, whenever this is duly justified and supported by a declaration of responsibility issued to that effect.

b) The amounts for the other items listed in the third clause, shall be paid quarterly in accordance with the implementation schedule of the study contained in the Protocol.

The payments outlined in the preceding paragraphs shall be made ​​upon issuance of the relevant invoices, by means of a bank transfer to the CCC ES12 0182 5566 71 0201512429 - Swift code: BBVAESMM - IBAN: ES12 0182 5566 7102 0151 2429, held by managing body, which will allocate them as set out in this contract.

SIX.- DURATION AND EFFECTIVENESS

This contract shall come into effect from the signing date, and shall continue in force until the completion of the study, the estimated duration of which is ______months, without prejudice to any obligations assumed by the parties which may remain in force after the completion thereof or following the early termination of the contract, as provided in the seventh clause.

In any case, any financial obligations arising from the performance of the study that may have accrued on the termination date of the contract shall remain in force, as shall the obligations regarding the protection of personal data and confidentiality of the information provided to conduct the study and obtained during the implementation thereof, including any other obligation arising from the performance of the study.

The parties know and accept that the study may only start once it has received a favourable report from the relevant Committee, the approval of the Management of the hospital and, where appropriate, the authorization of the competent regional or state agency, as applicable, according to the type of study. The effectiveness of this contract is subject to obtaining the said authorizations, with the sponsor being required to register the documents in the electronic record found on the web portal of the Ethics Committees of the Andalusian Public Health System.

SEVEN.- EARLY TERMINATION OF THE CONTRACT

The contract may be terminated early in the following cases:

- Mutual agreement between the parties.

- Breach of the obligations established under this contract, which is not remedied within thirty (30) days following receipt of a written notification from the party that has detected the breach, identifying the breach and demanding its remedy.

- Exceptionally, when an unforeseen circumstance attributable to the study leads to a significant deterioration in the health care activities of the department or unit.

- If any event or any other similar circumstance occurs in the study that makes it sensible not to continue with the implementation of the study, or should any other event occur that makes it impossible or inadvisable to continue with it.

In the event of early termination, the sponsor shall pay the amounts, as the case may be, corresponding to the work performed up to the date of the notification to the hospital by attested means, in accordance with the breakdown provided in the economic report.

EIGHT.- MONITOR ACCESS

The sponsor may appoint a monitor which, during each visit that it makes to the hospital, may access the relevant clinical documentation of the participants included in the study, under the supervision of the researchers and for the sole purpose of verifying the data provided by the latter in relation to compliance with the protocol, ensuring that the data are recorded correctly and in full, and making sure that the informed consent of all participants has been obtained before their inclusion in the study, as the case may be.

NINE.- CONFIDENTIALITY AND DATA PROTECTION

The parties undertake to use all the means at their disposal to guarantee the confidentiality of the information provided for the implementation of the study and obtained during the development thereof.

The personal data will be processed in accordance with the provisions of Organic Law 15/1999, of 13 December, on the protection of personal data, and its implementing regulations. Access to the clinical documentation of the participants in the study shall be conducted according to the provisions of Act 41/2002, of 14 November, regulating the bases of patient autonomy and the rights and obligations of clinical information and documents, and its implementing regulations.

The researcher shall treat the details of the participants as stipulated in the protocol. Only the people indicated on the information and informed consent sheet shall access the personal data of the participants.

The sponsor and researchers of the study must ensure the confidentiality of the data of the subjects and ensure that the provisions of Act 15/1999, of 13 December, on the protection of personal data, and its implementing regulations, are complied with at all times. In no case shall the name of the participants be disclosed if material from their medical records is used in publications deriving from this study.

TEN.- INTELLECTUAL AND INDUSTRIAL PROPERTY RIGHTS

The parties agree that all the rights to intellectual and industrial property, data, findings and discoveries or inventions, whether patentable or not, that may be made, obtained or produced in connection with the study, shall be the exclusive property of the sponsor and other institutions that the latter may determine, without prejudice to the rights that the law grants to researchers.

In the case of studies sponsored by the Andalusian Public Health System, the provisions of Decree 16/2012, of 7 February, shall be applicable, which regulate the management and transfer of the findings of activities of research, development and innovation whose ownership corresponds to agencies and other instrumental bodies dependent on the competent Ministry in the area of health, according to which the results of research, development and innovation activities carried out by the relevant personnel in their area of expertise shall belong to the agencies and instrumental bodies dependent on the competent health Ministry as labour inventions thereof.

When such data, findings, discoveries, inventions, methods and information are presented at scientific meetings or published in professional journals, provided the publication permits it, mention shall be made of the ______(name of the Hospital) as being the hospital that conducted the study, as well as the funds that made ​​it possible.